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The structural basis of function in Cys-loop receptors

Published online by Cambridge University Press:  20 September 2010

Andrew J. Thompson ,
Henry A. Lester  and
Sarah C. R. Lummis
Andrew J. Thompson
Affiliation:
Department of Biochemistry, University of Cambridge, Building O, Downing Site, Cambridge CB2 1QW, UK
Henry A. Lester
Affiliation:
California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA
Sarah C. R. Lummis*
Affiliation:
Department of Biochemistry, University of Cambridge, Building O, Downing Site, Cambridge CB2 1QW, UK
*
*Author for correspondence: Sarah C. R. Lummis, Department of Biochemistry, University of Cambridge, Building O Downing Site, Cambridge CB2 1QW, UK. Tel.: 01223 333600; Fax: 01223 333345; Email:sl120@cam.ac.uk
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Abstract

Cys-loop receptors are membrane-spanning neurotransmitter-gated ion channels that are responsible for fast excitatory and inhibitory transmission in the peripheral and central nervous systems. The best studied members of the Cys-loop family are nACh, 5-HT3, GABAA and glycine receptors. All these receptors share a common structure of five subunits, pseudo-symmetrically arranged to form a rosette with a central ion-conducting pore. Some are cation selective (e.g. nACh and 5-HT3) and some are anion selective (e.g. GABAA and glycine). Each receptor has an extracellular domain (ECD) that contains the ligand-binding sites, a transmembrane domain (TMD) that allows ions to pass across the membrane, and an intracellular domain (ICD) that plays a role in channel conductance and receptor modulation. Cys-loop receptors are the targets for many currently used clinically relevant drugs (e.g. benzodiazepines and anaesthetics). Understanding the molecular mechanisms of these receptors could therefore provide the catalyst for further development in this field, as well as promoting the development of experimental techniques for other areas of neuroscience.

In this review, we present our current understanding of Cys-loop receptor structure and function. The ECD has been extensively studied. Research in this area has been stimulated in recent years by the publication of high-resolution structures of nACh receptors and related proteins, which have permitted the creation of many Cys loop receptor homology models of this region. Here, using the 5-HT3 receptor as a typical member of the family, we describe how homology modelling and ligand docking can provide useful but not definitive information about ligand interactions. We briefly consider some of the many Cys-loop receptors modulators. We discuss the current understanding of the structure of the TMD, and how this links to the ECD to allow channel gating, and consider the roles of the ICD, whose structure is poorly understood. We also describe some of the current methods that are beginning to reveal the differences between different receptor states, and may ultimately show structural details of transitions between them.

Type
Review Article
Information
Quarterly Reviews of Biophysics , Volume 43 , Issue 4 , November 2010 , pp. 449 - 499
Copyright
Copyright © Cambridge University Press 2010

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References

10. References

Abdel-Halim, H., Hanrahan, J. R., Hibbs, D. E., Johnston, G. A. & Chebib, M. (2008). A molecular basis for agonist and antagonist actions at GABAC receptors. Chemical Biology and Drug Design 71, 306–327.CrossRefGoogle Scholar
Absalom, N. L., Schofield, P. R. & Lewis, T. M. (2009). Pore structure of the Cys-loop ligand-gated ion channels. Neurochemical Research 34, 1805–1815.CrossRefGoogle ScholarPubMed
Akabas, M. H. & Karlin, A. (1995). Identification of acetylcholine receptor channel-lining residues in the M1 segment of the α-subunit. Biochemistry 34, 12496–12500.Google Scholar
Akabas, M. H., Stauffer, D. A., Xu, M. & Karlin, A. (1992). Acetylcholine receptor channel structure probed in cysteine-substitution mutants. Science 258, 307–310.CrossRefGoogle ScholarPubMed
Akabas, M. H., Kaufmann, C., Archdeacon, P. & Karlin, A. (1994). Identification of acetylcholine receptor channel-lining residues in the entire M2 segment of the alpha subunit. Neuron 13, 919–927.CrossRefGoogle ScholarPubMed
Akk, G. & Steinbach, J. H. (2000). Structural elements near the C-terminus are responsible for changes in nicotinic receptor gating kinetics following patch excision. Journal of Physiology 527, 405–417.CrossRefGoogle ScholarPubMed
Amin, J., Brooks-Kayal, A. & Weiss, D. S. (1997). Two tyrosine residues on the alpha subunit are crucial for benzodiazepine binding and allosteric modulation of GABAA receptors. Molecular Pharmacology 51, 833–841.CrossRefGoogle Scholar
Arias, H. R. (Ed.) (2006). Biological and Biophysical Aspects of Ligand-gated Ion Channel Receptor Superfamilies. Kerala, India: Research Signpost.Google Scholar
Arias, H. R. & Bhumireddy, P. (2005). Anesthetics as chemical tools to study the structure and function of nicotinic acetylcholine receptors. Current Protein and Peptide Science 6, 451–472.Google Scholar
Arias, H. R. & Bouzat, C. (2006). Modulation of nicotinic acetylcholine receptors by noncompetitive antagonists. In Biological and Biophysical Aspects of Ligand-Gated Ion Channel Receptor Superfamilies (Ed. Arias, H. R.), Kerala, India: Research Signpost.Google Scholar
Auerbach, A. (2010). The gating isomerization of acetylcholine receptors. Journal of Physiology 588, 573–586.CrossRefGoogle ScholarPubMed
Bachy, A., Heaulme, M., Giudice, A., Michaud, J. C., Lefevre, I. A., Souilhac, J., Manara, L., Emerit, M. B., Gozlan, H., Hamon, M., Keane, P. E., Soubrie, P. & Lefure, G. (1993). SR 57227A: a potent and selective agonist at central and peripheral 5-HT3 receptors in vitro and in vivo. European Journal of Pharmacology 237, 299–309.Google Scholar
Baenziger, J. E. & Methot, N. (1995). Fourier transform infrared and hydrogen/deuterium exchange reveal an exchange-resistant core of alpha-helical peptide hydrogens in the nicotinic acetylcholine receptor. Journal of Biolical Chemistry 270, 29129–29137.CrossRefGoogle ScholarPubMed
Bafna, P. A., Purohit, P. G. & Auerbach, A. (2008). Gating at the mouth of the acetylcholine receptor channel: energetic consequences of mutations in the αM2-cap. PLoS ONE, 3, e2515.Google Scholar
Balduzzi, R., Cupello, A. & Robello, M. (2002). Modulation of the expression of GABAA receptors in rat cerebellar granule cells by protein tyrosine kinases and protein kinase C. Biochimica et Biophysica Acta 1564, 263–270.CrossRefGoogle ScholarPubMed
Bali, M. & Akabas, M. H. (2007). The location of a closed channel gate in the GABAA receptor channel. Journal of General Physiology 129, 145–159.CrossRefGoogle ScholarPubMed
Ballestero, J. A., Plazas, P. V., Kracun, S., Gomez-Casati, M. E., Taranda, J., Rothlin, C. V., Katz, E., Millar, N. S. & Elgoyhen, A. B. (2005). Effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors. Molecular Pharmacology 68: 822–829.Google Scholar
Barnes, N. M., Hales, T. G., Lummis, S. C. & Peters, J. A. (2009). The 5-HT3 receptor – the relationship between structure and function. Neuropharmacology 56, 273–284.CrossRefGoogle ScholarPubMed
Barrera, N. P., Herbert, P., Henderson, R. M., Martin, I. L. & Edwardson, J. M. (2005). Atomic force microscopy reveals the stoichiometry and subunit arrangement of 5-HT3 receptors. Proceedings of the National Academy of Sciences USA 102, 12595–12600.CrossRefGoogle Scholar
Bartos, M., Corradi, J. & Bouzat, C. (2009). Structural basis of activation of cys-loop receptors: the extracellular-transmembrane interface as a coupling region. Molecular Neurobiology 40, 236–252.Google Scholar
Baulac, S., Huberfeld, G., Gourfinkel-An, I., Mitropoulou, G., Beranger, A., Prud'Homme, J. F., Baulac, M., Brice, A., Bruzzone, R. & Leguern, E. (2001). First genetic evidence of GABAA receptor dysfunction in epilepsy: a mutation in the γ2-subunit gene. Nature Genetics 281, 46–48.CrossRefGoogle Scholar
Beato, M., Groot-Kormelink, P. J., Colquhoun, D. & Sivilotti, L. G. (2004). The activation mechanism of α1 homomeric glycine receptors. Journal of Neuroscience 24, 895–906.CrossRefGoogle ScholarPubMed
Beckstein, O., Biggin, P. C. & Sansom, M. S. P. (2001). A hyrdophobic gating mechanism for nanopores. Journal of Physical Chemistry B 105, 12902–12905.Google Scholar
Beene, D. L., Brandt, G. S., Zhong, W., Zacharias, N. M., Lester, H. A. & Dougherty, D. A. (2002). Cation–π interactions in ligand recognition by serotonergic (5-HT3A) and nicotinic acetylcholine receptors: the anomalous binding properties of nicotine. Biochemistry 4132, 10262–10269.Google Scholar
Beene, D. L., Price, K. L., Lester, H. A., Dougherty, D. A. & Lummis, S. C. (2004). Tyrosine residues that control binding and gating in the 5-hydroxytryptamine3 receptor revealed by unnatural amino acid mutagenesis. Journal of Neuroscience 24, 9097–9104.Google Scholar
Beg, A. A. & Jorgensen, E. M. (2003). EXP-1 is an excitatory GABA-gated cation channel. Nature Neuroscience 6, 1145–1152.Google Scholar
Bera, A. K., Chatav, M. & Akabas, M. H. (2002). GABAA receptor M2-M3 loop secondary structure and changes in accessibility during channel gating. Journal of Biological Chemistry 277, 43002–43010.CrossRefGoogle ScholarPubMed
Berezhnoy, D., Nyfeler, Y., Gonthier, A., Schwob, H., Goeldner, M. & Sigel, E. (2004). On the benzodiazepine binding pocket in GABAA receptors. Journal of Biological Chemistry 279, 3160–3168.CrossRefGoogle ScholarPubMed
Bertrand, D., Galzi, J. L., Devillers-Thiery, A., Bertrand, S. & Changeux, J. P. (1993). Mutations at two distinct sites within the channel domain M2 alter calcium permeability of neuronal α7 nicotinic receptor. Proceedings of the National Academy of Sciences USA 90, 6971–6975.Google Scholar
Bertrand, D., Bertrand, S., Cassar, S., Gubbins, E., Li, J. & Gopalakrishnan, M. (2008). Positive allosteric modulation of the α7 nAChR: ligand interactions with distinct binding sites and evidence for a prominent role of the M2–M3 segment 7 nAChR: ligand interactions with distinct binding sites and evidence for a prominent role of the M2–M3 segment. Molecular Pharmacology 74, 1407–1416.CrossRefGoogle Scholar
Bhattacharya, A., Dang, H., Zhu, Q. M., Schnegelsberg, B., Rozengurt, N., Cain, G., Prantil, R., Vorp, D. A., Guy, N., Julius, D., Ford, A. P., Lester, H. A. & Cockayne, D. A. (2004). Uropathic observations in mice expressing a constitutively active point mutation in the 5-HT3A receptor subunit. Journal of Neuroscience 24, 5537–5548.CrossRefGoogle ScholarPubMed
Bianchi, M. T., Haas, K. F. & Macdonald, R. L. (2001). Structural determinants of fast desensitization and desensitization-deactivation coupling in GABAa receptors. Journal of Neuroscience 21, 1127–1136.CrossRefGoogle ScholarPubMed
Blanton, M. P. & Cohen, J. B. (1992). Mapping the lipid-exposed regions in the Torpedo californica nicotinic acetylcholine receptor. Biochemistry 31, 3738–3750.Google Scholar
Blanton, M. P. & Cohen, J. B. (1994). Identifying the lipid–protein interface of the Torpedo nicotinic acetylcholine receptor: secondary structure implications. Biochemistry 33, 2859–2872.CrossRefGoogle ScholarPubMed
Blanton, M. P., Mccardy, E. A., Huggins, A. & Parikh, D. (1998). Probing the structure of the nicotinic acetylcholine receptor with the hydrophobic photoreactive probes [125I]TID-BE and [125I]TIDPC/16. Biochemistry 37, 14545–14555.CrossRefGoogle ScholarPubMed
Bocquet, N., Prado De Carvalho, L., Cartaud, J., Neyton, J., Le Poupon, C., Taly, A., Grutter, T., Changeux, J. P. & Corringer, P. J. (2007). A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family. Nature 445, 116–119.Google Scholar
Bocquet, N., Nury, H., Baaden, M., Le Poupon, C., Changeux, J. P., Delarue, M. & Corringer, P. J. (2009). X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation. Nature 457, 111–114.CrossRefGoogle Scholar
Boess, F. G., Steward, L. J., Steele, J. A., Liu, D., Reid, J., Glencorse, T. A. & Martin, I. L. (1997). Analysis of the ligand binding site of the 5-HT3 receptor using site directed mutagenesis: importance of glutamate 106. Neuropharmacology 36, 637–647.Google Scholar
Boileau, A. J. & Czajkowski, C. (1999). Identification of transduction elements for benzodiazepine modulation of the GABAA receptor: three residues are required for allosteric coupling. Journal of Neuroscience 19, 10213–10220.CrossRefGoogle ScholarPubMed
Bouzat, C., Bren, N. & Sine, S. M. (1994). Structural basis of the different gating kinetics of fetal and adult acetylcholine receptors. Neuron 13, 1395–1402.CrossRefGoogle ScholarPubMed
Bouzat, C., Roccamo, A. M., Garbus, I. & Barrantes, F. J. (1998). Mutations at lipid-exposed residues of the acetylcholine receptor affect its gating kinetics. Molecular Pharmacology 54, 146–153.Google Scholar
Bouzat, C., Barrantes, F. & Sine, S. (2000). Nicotinic receptor fourth transmembrane domain: hydrogen bonding by conserved threonine contributes to channel gating kinetics. Journal of General Physiology 115, 663–672.Google Scholar
Bouzat, C., Gumilar, F., Del Carmen Esandi, M. & Sine, S. M. (2002). Subunit-selective contribution to channel gating of the M4 domain of the nicotinic receptor. Biophysical Journal 82, 1920–1929.Google Scholar
Bouzat, C., Gumilar, F., Spitzmaul, G., Wang, H. L., Rayes, D., Hansen, S. B., Taylor, P. & Sine, S. M. (2004). Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel. Nature 430, 896–900.CrossRefGoogle Scholar
Bower, K. S., Price, K. L., Sturdee, L. E., Dayrell, M., Dougherty, D. A. & Lummis, S. C. (2008). 5-Fluorotryptamine is a partial agonist at 5-HT3 receptors, and reveals that size and electronegativity at the 5 position of tryptamine are critical for efficient receptor function. European Journal of Pharmacology 580, 291–297.Google Scholar
Boyd, G. W., Low, P., Dunlop, J. I., Robertson, L. A., Vardy, A., Lambert, J. J., Peters, J. A. & Connolly, C. N. (2002). Assembly and cell surface expression of homomeric and heteromeric 5-HT3 receptors: the role of oligomerization and chaperone proteins. Molecular and Cellular Neuroscience 21, 38–50.CrossRefGoogle ScholarPubMed
Brady, C. A., Stanford, I. M., Ali, I., Lin, L., Williams, J. M., Dubin, A. E., Hope, A. G. & Barnes, N. M. (2001). Pharmacological comparison of human homomeric 5-HT3A receptors versus heteromeric 5-HT3A/3B receptors. Neuropharmacology 41, 282–284.CrossRefGoogle ScholarPubMed
Brejc, K., Van Dijk, W. J., Klaassen, R. V., Schuurmans, M., Van Der Oost, J., Smit, A. B. & Sixma, T. K. (2001). Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors. Nature 411, 269–276.CrossRefGoogle ScholarPubMed
Broad, L. M., Felthouse, C., Zwart, R., Mcphie, G. I., Pearson, K. H., Craig, P. J., Wallace, L., Broadmore, R. J., Boot, J. R., Keenan, M., Baker, S. R. & Sher, E. (2002). PSAB-OFP, a selective α7 nicotinic receptor agonist, is also a potent agonist of the 5-HT3 receptor. European Journal of Pharmacology 452, 137–144.CrossRefGoogle Scholar
Broad, L. M., Zwart, R., Pearson, K. H., Lee, M., Wallace, L., Mcphie, G. I., Emkey, R., Hollinshead, S. P., Dell, C. P., Baker, S. R. & Sher, E. (2006). Identification and pharmacological profile of a new class of selective nicotinic acetylcholine receptor potentiators. Journal of Pharmacology and Experimental Therapeutics 318, 1108–1117.CrossRefGoogle ScholarPubMed
Brown, A. M., Hope, A. G., Lambert, J. J. & Peters, J. A. (1998). Ion permeation and conduction in a human recombinant 5-HT3 receptor subunit (h5-HT3A). Journal of Physiology 507, 653–665.CrossRefGoogle Scholar
Bruss, M., Barann, M., Hayer-Zillgen, M., Eucker, T., Gothert, M. & Bonisch, H. (2000). Modified 5-HT3A receptor function by co-expression of alternatively spliced human 5-HT3A receptor isoforms. Naunyn Schmiedebergs Archives of Pharmacology 362, 392–401.CrossRefGoogle ScholarPubMed
Butler, A. S., Lindesay, S. A., Dover, T. J., Kennedy, M. D., Patchell, V. B., Levine, B. A., Hope, A. G. & Barnes, N. M. (2009). Importance of the C-terminus of the human 5-HT3A receptor subunit. Neuropharmacology 56, 292–302.Google Scholar
Buhr, A., Baur, R. & Sigel, E. (1997a). Subtle changes in residue 77 of the gamma subunit of α1β2γ2 GABAA receptors drastically alter the affinity for ligands of the benzodiazepine binding site. Journal of Biolical Chemistry 272, 11799–11804.Google Scholar
Buhr, A., Schaerer, M. T., Baur, R. & Sigel, E. (1997b). Residues at positions 206 and 209 of the alpha1 subunit of GABAA receptors influence affinities for benzodiazepine binding site ligands. Molecular Pharmacology 52, 676–682.CrossRefGoogle ScholarPubMed
Buhr, A. & Sigel, E. (1997). A point mutation in the γ2 subunit of gamma-aminobutyric acid type A receptors results in altered benzodiazepine binding site specificity. Proceedings of the National Academy of Sciences USA 94, 8824–8829.CrossRefGoogle ScholarPubMed
Campos-Caro, A., Sala, S., Ballesta, J. J., Vicente-Agullo, F., Criado, M. & Sala, F. (1996). A single residue in the M2–M3 loop is a major determinant of coupling between binding and gating in neuronal nicotinic receptors. Proceedings of the National Academy of Sciences USA 93, 6118–6123.Google Scholar
Carland, J. E., Moorhouse, A. J., Barry, P. H., Johnston, G. A. & Chebib, M. (2004). Charged residues at the 2′ position of human GABAC ρ1 receptors invert ion selectivity and influence open state probability. Journal of Biological Chemistry 279, 54153–54160.CrossRefGoogle Scholar
Carland, J. E., Cooper, M. A., Sugiharto, S., Jeong, H. J., Lewis, T. M., Barry, P. H., Peters, J. A., Lambert, J. J. & Moorhouse, A. J. (2009). Characterization of the effects of charged residues in the intracellular loop on ion permeation in alpha1 glycine receptor channels. Journal of Biological Chemistry 284, 2023–2030.CrossRefGoogle ScholarPubMed
Cashin, A. L., Petersson, E. J., Lester, H. A. & Dougherty, D. A. (2005). Using physical chemistry to differentiate nicotinic from cholinergic agonists at the nicotinic acetylcholine receptor. Journal of the American Chemical Society 127, 350–356.Google Scholar
Castaldo, P., Stefanoni, P., Miceli, F., Coppola, G., Del Giudice, E. M., Bellini, G., Pascotto, A., Trudell, J. R., Harrison, N. L., Annunziato, L. & Taglialatela, M. (2004). A novel hyperekplexia-causing mutation in the pre-transmembrane segment 1 of the human glycine receptor α1 subunit reduces membrane expression and impairs gating by agonists. Journal of Biological Chemistry 279, 25598–25604.Google Scholar
Cederholm, J. M., Schofield, P. R. & Lewis, T. M. (2009). Gating mechanisms in Cys-loop receptors. European Biophysical Journal 39, 37–49.CrossRefGoogle ScholarPubMed
Celie, P. H., Van Rossum-Fikkert, S. E., Van Dijk, W. J., Brejc, K., Smit, A. B. & Sixma, T. K. (2004). Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures. Neuron 41, 907–914.CrossRefGoogle ScholarPubMed
Celie, P. H., Kasheverov, I. E., Mordvintsev, D. Y., Hogg, R. C., Van Nierop, P., Van Elk, R., Van Rossum-Fikkert, S. E., Zhmak, M. N., Bertrand, D., Tsetlin, V., Sixma, T. K. & Smit, A. B. (2005a). Crystal structure of nicotinic acetylcholine receptor homolog AChBP in complex with an α-conotoxin PnIA variant. Nature Structural and Molecular Biology 12, 582–588.CrossRefGoogle ScholarPubMed
Celie, P. H., Klaassen, R. V., Van Rossum-Fikkert, S. E., Van Elk, R., Van Nierop, P., Smit, A. B. & Sixma, T. K. (2005b). Crystal structure of acetylcholine-binding protein from Bulinus truncatus reveals the conserved structural scaffold and sites of variation in nicotinic acetylcholine receptors. Journal of Biological Chemistry 280, 26457–26466.CrossRefGoogle ScholarPubMed
Cens, T., Nargeot, J. & Charnet, P. (1997). Ca2+-permeability of muscle nicotinic acetylcholine receptor is increased by expression of the ε subunit. Receptors and Channels 5, 29–40.Google Scholar
Chakrapani, S., Bailey, T. D. & Auerbach, A. (2003). The role of loop 5 in acetylcholine receptor channel gating. Journal of General Physiology 122, 521–539.CrossRefGoogle ScholarPubMed
Champtiaux, N., Gotti, C., Cordero-Erausquin, M., David, D. J., Przybylski, C., Lena, C., Clementi, F., Moretti, M., Rossi, F. M., Le Novere, N., Mcintosh, J. M., Gardier, A. M. & Changeux, J. P. (2003). Subunit composition of functional nicotinic receptors in dopaminergic neurons investigated with knock-out mice. Journal of Neuroscience 23, 7820–7829.CrossRefGoogle ScholarPubMed
Chang, G., Spencer, R. H., Lee, A. T., Barclay, M. T. & Rees, D. C. (1998). Structure of the MscL homolog from Mycobacterium tuberculosis: a gated mechanosensitive ion channel. Science 282, 2220–2226.Google Scholar
Chang, Y. & Weiss, D. S. (1998). Substitutions of the highly conserved M2 leucine create spontaneously opening ρ1 gamma-aminobutyric acid receptors. Molecular Pharmacology 53, 511–523.CrossRefGoogle ScholarPubMed
Chang, Y. & Weiss, D. S. (2002). Site-specific fluorescence reveals distinct structural changes with GABA receptor activation and antagonism. Nature Neuroscience 5, 1163–1168.Google Scholar
Chang, Y. C., Wu, W., Zhang, J. L. & Huang, Y. (2009). Allosteric activation mechanism of the cys-loop receptors. Acta Pharmacolica Sinica 30, 663–672.Google Scholar
Changeux, J. P., Devillers-Thiery, A. & Chemouilli, P. (1984). Acetylcholine receptor: an allosteric protein. Science 225, 1335–1345.Google Scholar
Charnet, P., Labarca, C., Leonard, R. J., Vogelaar, N. J., Czyzyk, L., Gouin, A., Davidson, N. & Lester, H. A. (1990). An open-channel blocker interacts with adjacent turns of α-helices in the nicotinic acetylcholine receptor. Neuron 4, 87–95.CrossRefGoogle ScholarPubMed
Chen, L. (2010). In pursuit of the high-resolution structure of nicotinic acetylcholine receptors. Journal of Physiology 588, 557–564.CrossRefGoogle ScholarPubMed
Cohen, B. N., Labarca, C., Davidson, N. & Lester, H. A. (1992). Mutations in M2 alter the selectivity of the mouse nicotinic acetylcholine receptor for organic and alkali metal cations. Journal of General Physiology 100, 373–400.CrossRefGoogle ScholarPubMed
Connolly, C. N. (2008). Trafficking of 5-HT3 and GABAA receptors. Molecular Membrane Biology 25, 293–301.Google Scholar
Corbin, J., Methot, N., Wang, H. H., Baenziger, J. E. & Blanton, M. P. (1998). Secondary structure analysis of individual transmembrane segments of the nicotinic acetylcholine receptor by circular dichroism and Fourier transform infrared spectroscopy. Journal of Biological Chemistry 273, 771–777.Google Scholar
Corradi, J., Gumilar, F. & Bouzat, C. (2009). Single-channel kinetic analysis for activation and desensitization of homomeric 5-HT3A receptors. Biophysical Journal 97, 1335–1345.Google Scholar
Corringer, P. J., Bertrand, S., Galzi, J. L., Devillers-Thiery, A., Changeux, J. P. & Bertrand, D. (1999). Mutational analysis of the charge selectivity filter of the α7 nicotinic acetylcholine receptor. Neuron 22, 831–843.CrossRefGoogle ScholarPubMed
Corringer, P. J., Baaden, M., Bocquet, N., Delarue, M., Dufresne, V., Nury, H., Prevost, M. & Van Renterghem, C. (2010). Atomic structure and dynamics of pentameric ligand-gated ion channels: new insight from bacterial homologues. Journal of Physiology 588, 565–572.Google Scholar
Coultrap, S. J. & Machu, T. K. (2002). Enhancement of 5-hydroxytryptamine3A receptor function by phorbol 12-myristate, 13-acetate is mediated by protein kinase C and tyrosine kinase activity. Receptors Channels 8, 63–70.Google Scholar
Cromer, B. A., Morton, C. J. & Parker, M. W. (2002). Anxiety over GABAA receptor structure relieved by AChBP. Trends in Biochemical Science 27, 280–287.Google Scholar
Cruz-Martin, A., Mercado, J. L., Rojas, L. V., Mcnamee, M. G. & Lasalde-Dominicci, J. A. (2001). Tryptophan substitutions at lipid-exposed positions of the gamma M3 transmembrane domain increase the macroscopic ionic current response of the Torpedo californica nicotinic acetylcholine receptor. Journal of Membrane Biology 183, 61–70.CrossRefGoogle ScholarPubMed
Cully, D. F., Vassilatis, D. K., Liu, K. K., Paress, P. S., Van Der Ploeg, L. H., Schaeffer, J. M. & Arena, J. P. (1994). Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature 371, 707–711.Google Scholar
Cully, D. F., Paress, P. S., Liu, K. K., Schaeffer, J. M. & Arena, J. P. (1996). Identification of a Drosophila melanogaster glutamate-gated chloride channel sensitive to the antiparasitic agent avermectin. Journal of Biological Chemistry 271, 20187–20191.CrossRefGoogle Scholar
Cutting, G. R., Lu, L., O'Hara, B. F., Kasch, L. M., Montrose-Rafizadeh, C., Donovan, D. M., Shimada, S., Antonarakis, S. E., Guggino, W. B., Uhl, G. R. & et al. (1991). Cloning of the gamma-aminobutyric acid (GABA) ρ1 cDNA: a GABA receptor subunit highly expressed in the retina. Proceedings of the National Academy of Sciences USA 88, 2673–2677.Google Scholar
Cymes, G. D. & Grosman, C. (2008). Pore-opening mechanism of the nicotinic acetylcholine receptor evinced by proton transfer. Nature Structure and Molecular Biology 15, 389–396.CrossRefGoogle ScholarPubMed
Cymes, G. D., Ni, Y. & Grosman, C. (2005). Probing ion-channel pores one proton at a time. Nature 438, 975–980.Google Scholar
Dacosta, C. J. & Baenziger, J. E. (2009). A lipid-dependent uncoupled conformation of the acetylcholine receptor. Journal of Biological Chemistry 284, 17819–17825.Google Scholar
Dahan, D. S., Dibas, M. I., Petersson, E. J., Auyeung, V. C., Chanda, B., Bezanilla, F., Dougherty, D. A. & Lester, H. A. (2004). A fluorophore attached to nicotinic acetylcholine receptor β M2 detects productive binding of agonist to the alpha delta site. Proceedings of the National Academy of Sciences USA 101, 10195–10200.Google Scholar
Dang, H., England, P. M., Farivar, S. S., Dougherty, D. A. & Lester, H. A. (2000). Probing the role of a conserved M1 proline residue in 5- hydroxytryptamine(3) receptor gating. Molecular Pharmacology 57, 1114–1122.Google ScholarPubMed
Davies, P. A., Pistis, M., Hanna, M. C., Peters, J. A., Lambert, J. J., Hales, T. G. & Kirkness, E. F. (1999). The 5-HT3B subunit is a major determinant of serotonin-receptor function. Nature 397, 359–363.Google Scholar
Davies, P. A., Wang, W., Hales, T. G. & Kirkness, E. F. (2002). A novel class of ligand-gated ion channel is activated by Zn2+. Journal of Biological Chemistry 278, 712–717.CrossRefGoogle ScholarPubMed
De Planque, M. R., Rijkers, D. T., Liskamp, R. M. & Separovic, F. (2004). The α M1 transmembrane segment of the nicotinic acetylcholine receptor interacts strongly with model membranes. Magnetic Resonance Chemistry 42, 148–154.Google Scholar
De Rosa, M. J., Rayes, D., Spitzmaul, G. & Bouzat, C. (2002). Nicotinic receptor M3 transmembrane domain: position 8′ contributes to channel gating. Molecular Pharmacology 62, 406–414.CrossRefGoogle ScholarPubMed
Deane, C. M. & Lummis, S. C. (2001). The role and predicted propensity of conserved proline residues in the 5-HT3 receptor. Journal of Biological Chemistry 276, 37962–37966.Google Scholar
Deeb, T. Z., Carland, J. E., Cooper, M. A., Livesey, M. R., Lambert, J. J., Peters, J. A. & Hales, T. G. (2007). Dynamic modification of a mutant cytoplasmic cysteine residue modulates the conductance of the human 5-HT3A receptor. Journal of Biological Chemistry 282, 6172–6182.CrossRefGoogle ScholarPubMed
Dellisanti, C. D., Yao, Y., Stroud, J. C., Wang, Z. Z. & Chen, L. (2007). Crystal structure of the extracellular domain of nAChR α1 bound to α-bungarotoxin at 1·94 Å resolution. Nature Neuroscience 10, 953–962.CrossRefGoogle ScholarPubMed
Demuro, A. & Parker, I. (2005). “Optical patch-clamping”: single-channel recording by imaging Ca2+ flux through individual muscle acetylcholine receptor channels. Journal of General Physiology 126, 179–192.CrossRefGoogle ScholarPubMed
Derkach, V., Surprenant, A. & North, R. A. (1989). 5-HT3 receptors are membrane ion channels. Nature 339, 706–709.CrossRefGoogle ScholarPubMed
Dougherty, D. A. (2008). Cys-loop neuroreceptors: structure to the rescue? Chemical Reviews 108, 1642–1653.CrossRefGoogle ScholarPubMed
Drisdel, R. C., Manzana, E. & Green, W. N. (2004). The role of palmitoylation in functional expression of nicotinic α7 receptors. Journal of Neuroscience 24, 10502–10510.Google Scholar
Drisdel, R. C., Sharp, D., Henderson, T., Hales, T. G. & Green, W. N. (2008). High affinity binding of epibatidine to serotonin type 3 receptors. Journal of Biological Chemistry 283, 9659–9665.Google Scholar
Dubin, A. E., Huvar, R. D., Andrea, M. R., Pyati, J., Zhu, J. Y., Joy, K. C., Wilson, S. J., Galindo, J. E., Glass, C. A., Luo, L., Jackson, M. R., Lovenberg, T. W. & Erlander, M. G. (1999). The pharmacological and functional characteristics of the serotonin 5-HT3A receptor are specifically modified by a 5-HT3B receptor subunit. Journal of Biological Chemistry 274, 30799–30810.CrossRefGoogle Scholar
Dunne, E. L., Hosie, A. M., Wooltorton, J. R., Duguid, I. C., Harvey, K., Moss, S. J., Harvey, R. J. & Smart, T. G. (2002). An N-terminal histidine regulates Zn2+ inhibition on the murine GABAA receptor β3 subunit. British Journal of Pharmacology 137, 29–38.Google Scholar
Eddins, D., Lyford, L. K., Lee, J. W., Desai, S. A. & Rosenberg, R. L. (2002a). Permeant but not impermeant divalent cations enhance activation of nondesensitizing α7 nicotinic receptors. American Journal of Physiology – Cell Physiology 282, C796–C804.CrossRefGoogle ScholarPubMed
Eddins, D., Sproul, A. D., Lyford, L. K., Mclaughlin, J. T. & Rosenberg, R. L. (2002b). Glutamate 172, essential for modulation of L247T aα7 ACh receptors by Ca2+, lines the extracellular vestibule. American Journal of Physiology – Cell Physiology 283, C1454–1460.Google Scholar
Edelstein, S. J., Schaad, O., Henry, E., Bertrand, D. & Changeux, J. P. (1996). A kinetic mechanism for nicotinic acetylcholine receptors based on multiple allosteric transitions. Biological Cybernetics 75, 361–379.Google Scholar
Eiselé, J.-L., Bertrand, S., Galzi, J.-L., Devillers-Thiéry, A., Changeux, J.-P. & Bertrand, D. (1993). Chimaeric nicotinic-serotonergic receptor combines distinct ligand binding and channel specificities. Nature 366, 479–483.Google Scholar
Emerit, M. B., Doucet, E., Darmon, M. & Hamon, M. (2002). Native and cloned 5-HT3AS receptors are anchored to F-actin in clonal cells and neurons. Molecular and Cellular Neuroscience 20, 110–124.Google Scholar
Engblom, A. C., Carlson, B. X., Olsen, R. W., Schousboe, A. & Kristiansen, U. (2002). Point mutation in the first transmembrane region of the β2 subunit of the GABAA receptor alters desensitization kinetics of GABA and anesthetic-induced channel gating. Journal of Biological Chemistry 277, 17438–17447.Google Scholar
England, P. M., Zhang, Y., Dougherty, D. A. & Lester, H. A. (1999). Backbone mutations in transmembrane domains of a ligand-gated ion channel: implications for the mechanism of gating. Cell 96, 89–98.Google Scholar
Enz, R. & Cutting, G. R. (1999). GABAC receptor rho subunits are heterogeneously expressed in the human CNS and form homo- and heterooligomers with distinct physical properties. European Journal of Neuroscience 11, 41–50.CrossRefGoogle ScholarPubMed
Everitt, A. B., Seymour, V. A., Curmi, J., Laver, D. R., Gage, P. W. & Tierney, M. L. (2009). Protein interactions involving the γ2 large cytoplasmic loop of GABAA receptors modulate conductance. FASEB Journal 23, 4361–4369.Google Scholar
Faghih, R., Gopalakrishnan, M. & Briggs, C. A. (2008). Allosteric modulators of the α7 nicotinic acetylcholine receptor. Journal of Medicinal Chemistry 51, 701–712.CrossRefGoogle ScholarPubMed
Fatima-Shad, K. & Barry, P. H. (1993). Anion permeation in GABA- and glycine-gated channels of mammalian cultured hippocampal neurons. Proceedings of the Royal Society of London, Series B. Biological Science 253, 69–75.Google Scholar
Filatov, G. N. & White, M. M. (1995). The role of conserved leucines in the M2 domain of the acetylcholine receptor in channel gating. Molecular Pharmacology 48, 379–384.Google Scholar
Filippova, N., Sedelnikova, A., Zong, Y., Fortinberry, H. & Weiss, D. S. (2000). Regulation of recombinant GABAA and GABAC receptors by protein kinase C. Molecular Pharmacology 57, 847–856.Google Scholar
Filippova, N., Wotring, V. E. & Weiss, D. S. (2004). Evidence that the TM1-TM2 to the ρ1 GABA receptor pore. Journal of Biological Chemistry 279, 20906–20914.Google Scholar
Finer-Moore, J. & Stroud, R. M. (1984). Amphipathic analysis and possible formation of the ion channel in an acetylcholine receptor. Proceedings of the National Academy of Sciences USA 81, 155–159.Google Scholar
Fisher, J. L. (2002). A histidine residue in the extracellular N-terminal domain of the GABAA receptor α5 subunit regulates sensitivity to inhibition by zinc. Neuropharmacology 42, 922–928.Google Scholar
Fisher, J. L. & Macdonald, R. L. (1998). The role of an alpha subtype M2-M3 His in regulating inhibition of GABAA receptor current by zinc and other divalent cations. Journal of Neuroscience 18, 2944–2953.Google Scholar
Flood, P., Ramirez-Latorre, J. & Role, L. (1997). α4 β2 neuronal nicotinic acetylcholine receptors in the central nervous system are inhibited by isoflurane and propofol, but α7-type nicotinic acetylcholine receptors are unaffected. Anesthesiology 86, 859–865.Google Scholar
Fludzinski, P., Evrard, D. A., Bloomquist, W. E., Lacefield, W. B., Pfeifer, W., Jones, N. D., Deeter, J. B. & Cohen, M. L. (1987). Indazoles as indole bioisosteres: synthesis and evaluation of the tropanyl ester and amide of indazole-3-carboxylate as antagonists at the serotonin 5HT3 receptor. Journal of Medicinal Chemistry 30, 1535–1537.Google Scholar
Fujimoto, K., Yoshimura, Y., Ihara, M., Matsuda, K., Takeuchi, Y., Aoki, T. & Ide, T. (2008). Cy3–3-acylcholine: a fluorescent analogue of acetylcholine for single molecule detection. Bioorganic and Medicinal Chemistry Letters 18, 1106–1109.CrossRefGoogle ScholarPubMed
Gaimarri, A., Moretti, M., Riganti, L., Zanardi, A., Clementi, F. & Gotti, C. (2007). Regulation of neuronal nicotinic receptor traffic and expression. Brain Research Reviews 55, 134–143.CrossRefGoogle ScholarPubMed
Gallivan, J. P. & Dougherty, D. A. (1999). Cation-π interactions in structural biology. Proceedings of the National Academy of Sciences USA 96, 9459–9464.Google Scholar
Galzi, J. L., Devillers-Thiery, A., Hussy, N., Bertrand, S., Changeux, J. P. & Bertrand, D. (1992). Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic. Nature 359, 500–505.Google Scholar
Galzi, J. L., Bertrand, S., Corringer, P. J., Changeux, J. P. & Bertrand, D. (1996). Identification of calcium binding sites that regulate potentiation of a neuronal nicotinic acetylcholine receptor. EMBO Journal 15, 5824–5832.Google Scholar
Gao, F., Mer, G., Tonelli, M., Hansen, S. B., Burghardt, T. P., Taylor, P. & Sine, S. M. (2006). Solution NMR of acetylcholine binding protein reveals agonist-mediated conformational change of the C-loop. Molecular Pharmacology 70, 1230–1235.Google Scholar
Gay, E. A. & Yakel, J. L. (2007). Gating of nicotinic ACh receptors; new insights into structural transitions triggered by agonist binding that induce channel opening. Journal of Physiology 584, 727–733.Google Scholar
Gerzanich, V., Wang, F., Kuryatov, A. & Lindstrom, J. (1998). Alpha 5 subunit alters desensitization, pharmacology, Ca2+ permeability and Ca2+ modulation of human neuronal α 3 nicotinic receptors. Journal of Pharmacology and Experimental Therapeutics 286, 311–320.Google Scholar
Gill, C. H., Peters, J. A. & Lambert, J. J. (1995). An electrophysiological investigation of the properties of a murine recombinant 5-HT3 receptor stably expressed in HEK 293 cells. British Journal of Pharmacology 114, 1211–1221.Google Scholar
Gleitsman, K. R., Lester, H. A. & Dougherty, D. A. (2009). Probing the role of backbone hydrogen bonding in a critical beta sheet of the extracellular domain of a cys-loop receptor. Chembiochem 10, 1385–1391.Google Scholar
Goren, E. N., Reeves, D. C. & Akabas, M. H. (2004). Loose protein packing around the extracellular half of the GABAA receptor β1 subunit M2 channel-lining segment. Journal of Biological Chemistry 279, 11198–11205.Google Scholar
Görne-Tschelnokow, U., Strecker, A., Kaduk, C., Naumann, D. & Hucho, F. (1994). The transmembrane domains of the nicotinic acetylcholine receptor contain α-helical and β structures. EMBO Journal 13, 338–341.CrossRefGoogle ScholarPubMed
Gotti, C., Moretti, M., Gaimarri, A., Zanardi, A., Clementi, F. & Zoli, M. (2007). Heterogeneity and complexity of native brain nicotinic receptors. Biochemical Pharmacology 74, 1102–1111.Google Scholar
Grailhe, R., De Carvalho, L. P., Paas, Y., Le Poupon, C., Soudant, M., Bregestovski, P., Changeux, J. P. & Corringer, P. J. (2004). Distinct subcellular targeting of fluorescent nicotinic α 3 β 4 and serotoninergic 5-HT3A receptors in hippocampal neurons. European Journal of Neuroscience 19, 855–862.Google Scholar
Green, T., Stauffer, K. A. & Lummis, S. C. (1995). Expression of recombinant homo-oligomeric 5-hydroxytryptamine3 receptors provides new insights into their maturation and structure. Journal of Biological Chemistry 270, 6056–6061.Google Scholar
Greenfield, L. J. Jr., Zaman, S. H., Sutherland, M. L., Lummis, S. C., Niemeyer, M. I., Barnard, E. A. & Macdonald, R. L. (2002). Mutation of the GABAA receptor M1 transmembrane proline increases GABA affinity and reduces barbiturate enhancement. Neuropharmacology 42, 502–521.CrossRefGoogle ScholarPubMed
Gronlien, J. H., Hakerud, M., Ween, H., Thorin-Hagene, K., Briggs, C. A., Gopalakrishnan, M. & Malysz, J. (2007). Distinct profiles of α7 nAChR positive allosteric modulation revealed by structurally diverse chemotypes. Molecular Pharmacology 72, 715–724.CrossRefGoogle ScholarPubMed
Grosman, C., Salamone, F. N., Sine, S. M. & Auerbach, A. (2000a). The extracellular linker of muscle acetylcholine receptor channels is a gating control element. Journal of General Physiology 116, 327–340.Google Scholar
Grosman, C., Zhou, M. & Auerbach, A. (2000b). Mapping the conformational wave of acetylcholine receptor channel gating. Nature 403(6771), 773–776.Google Scholar
Grutter, T., De Carvalho, L. P., Dufresne, V., Taly, A., Edelstein, S. J. & Changeux, J. P. (2005a). Molecular tuning of fast gating in pentameric ligand-gated ion channels. Proceedings of the National Academy of Sciences USA 102, 18207–18212.Google Scholar
Grutter, T., Prado De Carvalho, L., Virginie, D., Taly, A., Fischer, M. & Changeux, J. P. (2005b). A chimera encoding the fusion of an acetylcholine-binding protein to an ion channel is stabilized in a state close to the desensitized form of ligand-gated ion channels. Comptes Rendus Biologies 328, 223–234.Google Scholar
Gunthorpe, M. J. & Lummis, S. C. R. (2001). Conversion of the ion selectivity of the 5-HT3A receptor from cationic to anionic reveals a conserved feature of the ligand-gated ion channel superfamily. Journal of Biological Chemistry 276, 21990.Google Scholar
Gurley, D. A. & Lanthorn, T. H. (1998). Nicotinic agonists competitively antagonize serotonin at mouse 5-HT3 receptors expressed in Xenopus oocytes. Neuroscience Letters 247, 107–110.CrossRefGoogle ScholarPubMed
Guzman, G. R., Santiago, J., Ricardo, A., Marti-Arbona, R., Rojas, L. V. & Lasalde-Dominicci, J. A. (2003). Tryptophan scanning mutagenesis in the α M3 transmembrane domain of the Torpedo californica acetylcholine receptor: functional and structural implications. Biochemistry 42, 12243–12250.Google Scholar
Haeger, S., Kuzmin, D., Detro-Dassen, S., Lang, N., Kilb, M., Tsetlin, V., Betz, H., Laube, B. & Schmalzing, G. (2010). An intramembrane aromatic network determines pentameric assembly of Cys-loop receptors. Nature Structural and Molecular Biology 17, 90–98.Google Scholar
Hales, T. G., Dunlop, J. I., Deeb, T. Z., Carland, J. E., Kelley, S. P., Lambert, J. J. & Peters, J. A. (2006). Common determinants of single channel conductance within the large cytoplasmic loop of 5-hydroxytryptamine type 3 and α4β2 nicotinic acetylcholine receptors. Journal of Biological Chemistry 281, 8062–8071.Google Scholar
Hanek, A. P., Lester, H. A. & Dougherty, D. A. (2010). Photochemical proteolysis of an unstructured linker of the GABAAR extracellular domain prevents GABA but not pentobarbital activation. Molecular Pharmacology 78(1), 29–35.Google Scholar
Hansen, S. B., Sulzenbacher, G., Huxford, T., Marchot, P., Taylor, P. & Bourne, Y. (2005). Structures of Aplysia AChBP complexes with nicotinic agonists and antagonists reveal distinctive binding interfaces and conformations. EMBO Journal 24, 3635–3646.Google Scholar
Hansen, S. B. & Taylor, P. (2007). Galanthamine and non-competitive inhibitor binding to ACh-binding protein: evidence for a binding site on non-alpha-subunit interfaces of heteromeric neuronal nicotinic receptors. Journal of Molecular Biology 369, 895–901.Google Scholar
Hanson, S. M. & Czajkowski, C. (2008). Structural mechanisms underlying benzodiazepine modulation of the GABAA receptor. Journal of Neuroscience 28, 3490–3499.Google Scholar
Hawthorne, R. & Lynch, J. W. (2006). The molecular pharmacology of the glycine receptor. In Biological and Biophysical Aspects of Ligand-Gated Ion Channel Receptor Superfamilies (Ed. Arias, H. R.), pp. 35836–35843. Kerala, India: Research Signpost.Google Scholar
Hibbs, R. E., Sulzenbacher, G., Shi, J., Talley, T. T., Conrod, S., Kem, W. R., Taylor, P., Marchot, P. & Bourne, Y. (2009). Structural determinants for interaction of partial agonists with acetylcholine binding protein and neuronal α7 nicotinic acetylcholine receptor. Embo Journal 28, 3040–3051.Google Scholar
Hilf, R. J. & Dutzler, R. (2008). X-ray structure of a prokaryotic pentameric ligand-gated ion channel. Nature 452, 375–379.Google Scholar
Hogg, R. C. & Bertrand, D. (2007). Partial agonists as therapeutic agents at neuronal nicotinic acetylcholine receptors. Biochemical Pharmacology 73, 459–468.CrossRefGoogle ScholarPubMed
Hogg, R. C., Raggenbass, M. & Bertrand, D. (2003). Nicotinic acetylcholine receptors: from structure to brain function. Reviews of Physiology, Biochemistry and Pharmacology 147, 1–46.Google Scholar
Holbrook, J. D., Gill, C. H., Zebda, N., Spencer, J. P., Leyland, R., Rance, K. H., Trinh, H., Balmer, G., Kelly, F. M., Yusaf, S. P., Courtenay, N., Luck, J., Rhodes, A., Modha, S., Moore, S. E., Sanger, G. J. & Gunthorpe, M. J. (2009). Characterisation of 5-HT3C, 5-HT3D and 5-HT3E receptor subunits: evolution, distribution and function. Journal of Neurochemistry 108, 384–396.Google Scholar
Horenstein, J. & Akabas, M. H. (1998). Location of a high affinity Zn2+ binding site in the channel of α1β1 GABAA receptors. Molecular Pharmacology 53, 870–877.Google Scholar
Horenstein, J., Wagner, D., Czajkowski, C. & Akabas, M. (2001). Protein mobility and GABA-induced conformational changes in GABAA receptor pore-lining M2 segment. Nature Neuroscience 4, 477–485.CrossRefGoogle ScholarPubMed
Hosie, A. M., Dunne, E. L., Harvey, R. J. & Smart, T. G. (2003). Zinc-mediated inhibition of GABAA receptors: discrete binding sites underlie subtype specificity. Nature Neuroscience 6, 362–369.Google Scholar
Hovius, R., Schmid, E. L., Tairi, A. P., Blasey, H., Bernard, A. R., Lundstrom, K. & Vogel, H. (1999). Fluorescence techniques for fundamental and applied studies of membrane protein receptors: the 5-HT3 serotonin receptor. Journal of Receptor Signal and Transduction Research 19, 533–545.Google Scholar
Hsiao, B., Mihalak, K. B., Repicky, S. E., Everhart, D., Mederos, A. H., Malhotra, A. & Luetje, C. W. (2006). Determinants of zinc potentiation on the α4 subunit of neuronal nicotinic receptors. Molecular Pharmacology 69, 27–36.Google Scholar
Hu, X. Q. & Lovinger, D. M. (2005). Role of aspartate 298 in mouse 5-HT3A receptor gating and modulation by extracellular Ca2+. Journal of Physiology 568, 381–396.Google Scholar
Hu, X. Q. & Peoples, R. W. (2008). The 5-HT3B subunit confers spontaneous channel opening and altered ligand properties of the 5-HT3 receptor. Journal of Biological Chemistry 283, 6826–6831.Google Scholar
Hu, X. Q., Zhang, L., Stewart, R. R. & Weight, F. F. (2003). Arginine 222 in the pre-transmembrane domain 1 of 5-HT3A receptors links agonist binding to channel gating. Journal of biological Chemistry 278, 46583–46589.Google Scholar
Huang, R.-Q., Gonzales, E. B. & Dillon, G. H. (2006). GABAA receptors: structure, function and modulation. In Biological and Biophysical Aspects of Ligand-Gated Ion Channel Receptor Superfamilies (Ed. Arias, H. R.), pp. 171–198. Kerala, India: Research Signpost.Google Scholar
Hubbard, P. C. & Lummis, S. C. (2000). Zn2+ enhancement of the recombinant 5-HT(3) receptor is modulated by divalent cations. European Journal of Pharmacology 394, 189–197.Google Scholar
Hubbard, P. C., Thompson, A. J. & Lummis, S. C. (2000). Functional differences between splice variants of the murine 5-HT3A receptor: possible role for phosphorylation. Brain Research and Molecular Brain Research 81, 101–108.Google Scholar
Hummer, G., Rasaiah, J. C. & Noworyta, J. P. (2001). Water conduction through the hydrophobic channel of a carbon nanotube. Nature 414, 188–190.Google Scholar
Hussy, N., Lukas, W. & Jones, K. A. (1994). Functional properties of a cloned 5-hydroxytryptamine ionotropic receptor subunit: comparison with native mouse receptors. Journal of Physiology 481, 311–323.Google Scholar
Ilegems, E., Pick, H. M., Deluz, C., Kellenberger, S. & Vogel, H. (2004). Noninvasive imaging of 5-HT3 receptor trafficking in live cells: from biosynthesis to endocytosis. Journal of Biological Chemistry 279, 53346–53352.Google Scholar
Jackson, M. B. (1984). Spontaneous openings of the acetylcholine receptor channel. Proceedings of the National Academy of Sciences USA 81, 3901–3904.Google Scholar
Jackson, M. B. (1986). Kinetics of unliganded acetylcholine receptor channel gating. Biophysical Journal 49(3), 663–672.Google Scholar
Jansen, M., Bali, M. & Akabas, M. H. (2008). Modular design of Cys-loop ligand-gated ion channels: functional 5-HT3 and GABA ρ1 receptors lacking the large cytoplasmic M3M4 loop. Journal of General Physiology 131, 137–146.Google Scholar
Jensen, A. A., Davies, P. A., Brauner-Osborne, H. & Krzywkowski, K. (2008). 3B but which 3B? And that's just one of the questions: the heterogeneity of human 5-HT(3) receptors. Trends in Pharmacological Science 29, 437–444.Google Scholar
Jensen, M. L., Pedersen, L. N., Timmermann, D. B., Schousboe, A. & Ahring, P. K. (2005a). Mutational studies using a cation-conducting GABAA receptor reveal the selectivity determinants of the Cys-loop family of ligand-gated ion channels. Journal of Neurochemistry 92, 962–972.CrossRefGoogle ScholarPubMed
Jensen, M. L., Schousboe, A. & Ahring, P. K. (2005b). Charge selectivity of the Cys-loop family of ligand-gated ion channels. Journal of Neurochemistry 92, 217–225.Google Scholar
Jensen, M. L., Timmermann, D. B., Johansen, T. H., Schousboe, A., Varming, T. & Ahring, P. K. (2002). The β subunit determines the ion selectivity of the GABAA receptor. Journal of Biological Chemistry 277, 41438–41447.Google Scholar
Jones-Davis, D. M., Song, L., Gallagher, M. J. & Macdonald, R. L. (2005). Structural determinants of benzodiazepine allosteric regulation of GABAA receptor currents. Journal of Neuroscience 25, 8056–8065.Google Scholar
Joshi, P. R., Suryanarayanan, A., Hazai, E., Schulte, M. K., Maksay, G. & Bikadi, Z. (2006). Interactions of granisetron with an agonist-free 5-HT3A receptor model. Biochemistry 45, 1099–1105.Google Scholar
Kaneez, F. S. & White, M. (2004). Patch clamp study of serotonin-gated currents via 5-HT type 3 receptors by using a novel approach SHAM for receptor channel scanning. Journal of Biomedical Biotechnology 1, 10–15.Google Scholar
Kapur, J. & Macdonald, R. L. (1997). Rapid seizure-induced reduction of benzodiazepine and Zn2+ sensitivity of hippocampal dentate granule cell GABAA receptors. Journal of Neuroscience 17, 7532–7540.Google Scholar
Karlin, A., Holtzman, E., Yodh, N., Lobel, P., Wall, J. & Hainfeld, J. (1983). The arrangement of the subunits of the acetylcholine receptor of Torpedo californica. Journal of Biological Chemistry 258, 6678–6681.Google Scholar
Kash, T. L., Dizon, M. J., Trudell, J. R. & Harrison, N. L. (2004). Charged residues in the β2 subunit involved in GABAA receptor activation. Journal of Biological Chemistry 279, 4887–4893.Google Scholar
Kash, T. L., Jenkins, A., Kelley, J. C., Trudell, J. R. & Harrison, N. L. (2003). Coupling of agonist binding to channel gating in the GABAA receptor. Nature 421, 272–275.Google Scholar
Kelley, S. P., Dunlop, J. I., Kirkness, E. F., Lambert, J. J. & Peters, J. A. (2003). A cytoplasmic region determines single-channel conductance in 5-HT3 receptors. Nature 424, 321–324.Google Scholar
Keramidas, A., Moorhouse, A. J., French, C. R., Schofield, P. R. & Barry, P. H. (2000). M2 pore mutations convert the glycine receptor channel from being anion- to cation-selective. Biophysical Journal 79, 247–259.Google Scholar
Keramidas, A., Moorhouse, A. J., Pierce, K. D., Schofield, P. R. & Barry, P. H. (2002). Cation-selective mutations in the M2 domain of the inhibitory glycine receptor channel reveal determinants of ion-charge selectivity. Journal of General Physiology 119, 393–410.Google Scholar
Keramidas, A., Moorhouse, A. J., Schofield, P. R. & Barry, P. H. (2004). Ligand-gated ion channels: mechanisms underlying ion selectivity. Progress in Biophysics and Molecular Biology 86, 161–204.Google Scholar
Kneussel, M. & Loebrich, S. (2007). Trafficking and synaptic anchoring of ionotropic inhibitory neurotransmitter receptors. Biology of the Cell 99, 297–309.Google Scholar
Konno, T., Busch, C., Von Kitzing, E., Imoto, K., Wang, F., Nakai, J., Mishina, M., Numa, S. & Sakmann, B. (1991). Rings of anionic amino acids as structural determinants of ion selectivity in the acetylcholine receptor channel. Proceedings of the Royal Society of London B: Biological Science 244, 69–79.Google Scholar
Korpi, E. R., Grunder, G. & Luddens, H. (2002). Drug interactions at GABAA receptors. Progress in Neurobiology 67, 113–159.Google Scholar
Kucken, A. M., Wagner, D. A., Ward, P. R., Teissere, J. A., Boileau, A. J. & Czajkowski, C. (2000). Identification of benzodiazepine binding site residues in the γ2 subunit of the GABAA receptor. Molecular Pharmacology 57, 932–939.Google Scholar
Kusama, T., Wang, J. B., Spivak, C. E. & Uhl, G. R. (1994). Mutagenesis of the GABA ρ1 receptor alters agonist affinity and channel gating. Neuroreport 5, 1209–1212.Google Scholar
Labarca, C., Nowak, M. W., Zhang, H., Tang, L., Deshpande, P. & Lester, H. A. (1995). Channel gating governed symmetrically by conserved leucine residues in the M2 domain of nicotinic receptors. Nature 376, 514–516.Google Scholar
Lambert, J. J., Peters, J. A., Hales, T. G. & Dempster, J. (1989). The properties of 5-HT3 receptors in clonal cell lines studied by patch-clamp techniques. British Journal of Pharmacology 97, 27–40.Google Scholar
Lankiewicz, S., Huser, M. B., Heumann, R., Hatt, H. & Gisselmann, G. (2000). Phosphorylation of the 5-hydroxytryptamine3 (5-HT3) receptor expressed in HEK293 cells. Receptors Channels 7, 9–15.Google Scholar
Lape, R., Colquhoun, D. & Sivilotti, L. G. (2008). On the nature of partial agonism in the nicotinic receptor superfamily. Nature 454, 722–727.Google Scholar
Lasalde, J. A., Tamamizu, S., Butler, D. H., Vibat, C. R., Hung, B. & Mcnamee, M. G. (1996). Tryptophan substitutions at the lipid-exposed transmembrane segment M4 of Torpedo californica acetylcholine receptor govern channel gating. Biochemistry 35, 14139–14148.Google Scholar
Law, R. J., Forrest, L. R., Ranatunga, K. M., La Rocca, P., Tieleman, D. P. & Sansom, M. S. (2000). Structure and dynamics of the pore-lining helix of the nicotinic receptor: MD simulations in water, lipid bilayers, and transbilayer bundles. Proteins 39, 47–55.Google Scholar
Le Novere, N., Grutter, T. & Changeux, J. P. (2002). Models of the extracellular domain of the nicotinic receptors and of agonist- and Ca2+-binding sites. Proceedings of the National Academy of Sciences USA 99, 3210–3215.Google Scholar
Lee, Y. H., Li, L., Lasalde, J., Rojas, L., Mcnamee, M., Ortiz-Miranda, S. I. & Pappone, P. (1994). Mutations in the M4 domain of Torpedo californica acetylcholine receptor dramatically alter ion channel function. Biophysical Journal 66, 646–653.Google Scholar
Lee, W. Y., Free, C. R. & Sine, S. M. (2008). Nicotinic receptor interloop proline anchors β1–β2 and Cys loops in coupling agonist binding to channel gating. Journal of General Physiology 132, 265–278.Google Scholar
Lee, W. Y., Free, C. R. & Sine, S. M. (2009). Binding to gating transduction in nicotinic receptors: Cys-loop energetically couples to pre-M1 and M2–M3 regions. Journal of Neuroscience 29, 3189–3199.Google Scholar
Lee, W. Y. & Sine, S. M. (2005). Principal pathway coupling agonist binding to channel gating in nicotinic receptors. Nature 438, 243–247.Google Scholar
Leite, J. F., Blanton, M. P., Shahgholi, M., Dougherty, D. A. & Lester, H. A. (2003). Conformation-dependent hydrophobic photolabeling of the nicotinic receptor: electrophysiology-coordinated photochemistry and mass spectrometry. Proceedings of the National Academy of Sciences USA 100, 13054–13059.Google Scholar
Leonard, R. J., Labarca, C. G., Charnet, P., Davidson, N. & Lester, H. A. (1988). Evidence that the M2 membrane-spanning region lines the ion channel pore of the nicotinic receptor. Science 242, 1578–1581.Google Scholar
Lester, H. A. (1992). The permeation pathway of neurotransmitter-gated ion channels. Annual Review of Biophysics and Biomolecular Structure 21, 267–292.Google Scholar
Lewis, T. M., Sivilotti, L. G., Colquhoun, D., Gardiner, R. M., Schoepfer, R. & Rees, M. (1998). Properties of human glycine receptors containing the hyperekplexia mutation alpha1(K276E), expressed in Xenopus oocytes. Journal of Physiology 507, 25–40.CrossRefGoogle ScholarPubMed
Li, P., Slimko, E. M. & Lester, H. A. (2002). Selective elimination of glutamate activation and introduction of fluorescent proteins into a Caenorhabditis elegans chloride channel. FEBS Letters 528, 77–82.Google Scholar
Limapichat, W., Lester, H. A. & Dougherty, D. A. (2010). Chemical scale studies of the Phe-Pro conserved motif in the Cys loop of Cys loop receptors. Journal of Biolical Chemistry 285, 8976–8984.Google Scholar
Livesey, M. R., Cooper, M. A., Deeb, T. Z., Carland, J. E., Kozuska, J., Hales, T. G., Lambert, J. J. & Peters, J. A. (2008). Structural determinants of Ca2+ permeability and conduction in the human 5-hydroxytryptamine type 3A receptor. Journal of Biological Chemistry 283, 19301–19313.Google Scholar
Lobitz, N., Gisselmann, G., Hatt, H. & Wetzel, C. H. (2001). A single amino-acid in the TM1 domain is an important determinant of the desensitization kinetics of recombinant human and guinea pig alpha-homomeric 5-hydroxytryptamine type 3 receptors. Molecular Pharmacology 59, 844–851.Google Scholar
Lobo, I. A., Mascia, M. P., Trudell, J. R. & Harris, R. A. (2004). Channel gating of the glycine receptor changes accessibility to residues implicated in receptor potentiation by alcohols and anesthetics. Journal of Biological Chemistry 297, 33919–33927.Google Scholar
Lochner, M. & Lummis, S. C. (2010). Agonists and antagonists bind to an A–A interface in the heteromeric 5-HT3AB receptor. Biophysical Journal 98, 1494–1502.Google Scholar
Lopes, C., Pereira, E. F., Wu, H. Q., Purushottamachar, P., Njar, V., Schwarcz, R. & Albuquerque, E. X. (2007). Competitive antagonism between the nicotinic allosteric potentiating ligand galantamine and kynurenic acid at α7 nicotinic receptors. Journal of Pharmacology and Experimental Therapeutics 322, 48–58.Google Scholar
Lugovskoy, A. A., Maslennikov, I. V., Utkin, Y. N., Tsetlin, V. I., Cohen, J. B. & Arseniev, A. S. (1998). Spatial structure of the M3 transmembrane segment of the nicotinic acetylcholine receptor α subunit. European Journal of Biochemistry 255, 455–461.Google Scholar
Lummis, S. C., Beene, D. L., Harrison, N. J., Lester, H. A. & Dougherty, D. A. (2005a). A cation–π binding interaction with a tyrosine in the binding site of the GABAC receptor. Chemistry &l Biology 12, 993–997.Google Scholar
Lummis, S. C., Beene, D. L., Lee, L. W., Lester, H. A., Broadhurst, R. W. & Dougherty, D. A. (2005b). Cis-trans isomerization at a proline opens the pore of a neurotransmitter-gated ion channel. Nature 438, 248–252.Google Scholar
Lynch, J. W. (2004). Molecular structure and function of the glycine receptor chloride channel. Physiological Reviews 84, 1051–1095.Google Scholar
Lynch, J. W. (2009). Native glycine receptor subtypes and their physiological roles. Neuropharmacology 56, 303–309.Google Scholar
Lynch, J. W., Rajendra, S., Pierce, K. D., Handford, C. A., Barry, P. H. & Schofield, P. R. (1997). Identification of intracellular and extracellular domains mediating signal transduction in the inhibitory glycine receptor chloride channel. EMBO Journal 16, 110–120.Google Scholar
Lynch, J. W., Han, N. L., Haddrill, J., Pierce, K. D. & Schofield, P. R. (2001). The surface accessibility of the glycine receptor M2–M3 loop is increased in the channel open state. Journal of Neuroscience 21, 2589–2599.Google Scholar
Ma, D., Liu, Z., Li, L., Tang, P. & Xu, Y. (2005). Structure and dynamics of the second and third transmembrane domains of human glycine receptor. Biochemistry 44, 8790–8800.Google Scholar
Machu, T. K. & Harris, R. A. (1994). Alcohols and anesthetics enhance the function of 5-hydroxytryptamine3 receptors expressed in Xenopus laevis oocytes. Journal of Pharmacology and Experimental Therapeutics 271, 898–905.Google Scholar
Macor, J. E., Gurley, D., Lanthorn, T., Loch, J., Mack, R. A., Mullen, G., Tran, O., Wright, N. & Gordon, J. C. (2001). The 5-HT3 antagonist tropisetron (ICS 205–930) is a potent and selective alpha7 nicotinic receptor partial agonist. Bioorganic and Medicinal Chemical Letters 11, 319–321.Google Scholar
Maksay, G., Bikadi, Z. & Simonyi, M. (2003). Binding interactions of antagonists with 5-hydroxytryptamine3A receptor models. Journal of Receptor Signal and Transduction Research 23, 255–270.Google Scholar
Malone, H. M., Peters, J. A. & Lambert, J. J. (1991). Physiological and pharmacological properties of 5-HT3 receptors – a patch-clamp study. Neuropeptides 19(Suppl), 25–30.Google Scholar
Mcdonald, B. J. & Moss, S. J. (1994). Differential phosphorylation of intracellular domains of GABAA receptor subunits by calcium/calmodulin type 2-dependent protein kinase and cGMP-dependent protein kinase. Journal of Biological Chemistry 269, 18111–18117.Google Scholar
Mcdonald, B. J. & Moss, S. J. (1997). Conserved phosphorylation of the intracellular domains of GABAA receptor β2 and β3 subunits by cAMP-dependent protein kinase, cGMP-dependent protein kinase protein kinase C and Ca2+/calmodulin type II-dependent protein kinase. Neuropharmacology 36, 1377–1385.Google Scholar
Mckernan, R. M., Farrar, S., Collins, I., Emms, F., Asuni, A., Quirk, K. & Broughton, H. (1998). Photoaffinity labeling of the benzodiazepine binding site of α1β3γ2 GABAA receptors with flunitrazepam identifies a subset of ligands that interact directly with His102 of the alpha subunit and predicts orientation of these within the benzodiazepine pharmacophore. Molecular Pharmacology 54, 33–43.Google Scholar
Melis, C., Lummis, S. C. & Molteni, C. (2008). Molecular dynamics simulations of GABA binding to the GABAC receptor: the role of Arg104. Biophysical Journal 95, 4115–4123.Google Scholar
Melzer, N., Villmann, C., Becker, K., Harvey, K., Harvey, R. J., Vogel, N., Kluck, C. J., Kneussel, M. & Becker, C. M. (2010). Multifunctional basic motif in the glycine receptor intracellular domain induces subunit-specific sorting. Journal of Biological Chemistry 285, 3730–3739.Google Scholar
Menard, C., Horvitz, H. R., Cannon, S. (2005). Chimeric mutations in the M2 segment of the 5-hydroxytryptamine-gated chloride channel MOD-1 define a minimal determinant of anion/cation permeability. Journal of Biological Chemistry 280, 27502–27507.Google Scholar
Methot, N., Mccarthy, M. P. & Baenziger, J. E. (1994). Secondary structure of the nicotinic acetylcholine receptor: implications for structural models of a ligand-gated ion channel. Biochemistry 33, 7709–7717.Google Scholar
Mihic, S. J., Whiting, P. J., Klein, R. L., Wafford, K. A. & Harris, R. A. (1994). A single amino acid of the human GABAA receptor γ2 subunit determines benzodiazepine efficacy. Journal of Biological Chemistry 269, 32768–32773.Google Scholar
Millar, N. S. (2008). RIC-3: a nicotinic acetylcholine receptor chaperone. British Journal of Pharmacology 153(Suppl. 1), S177–183.Google Scholar
Millar, N. S. & Harkness, P. C. (2008). Assembly and trafficking of nicotinic acetylcholine receptors. Molecular Membrane Biology 25, 279–292.CrossRefGoogle ScholarPubMed
Miller, J. C., Silverman, S. K., England, P. M., Dougherty, D. A. & Lester, H. A. (1998). Flash decaging of tyrosine sidechains in an ion channel. Neuron 20, 619–624.Google Scholar
Millar, N. S. & Gotti, C. (2009). Diversity of vertebrate nicotinic acetylcholine receptors. Neuropharmacology 56, 237–246.Google Scholar
Miyazawa, A., Fujiyoshi, Y., Stowell, M. & Unwin, N. (1999). Nicotinic acetylcholine receptor at 4·6 Å resolution: transverse tunnels in the channel wall. Journal of Molecular Biology 288, 765–786.Google Scholar
Miyazawa, A., Fujiyoshi, Y. & Unwin, N. (2003). Structure and gating mechanism of the acetylcholine receptor pore. Nature 424, 949–955.Google Scholar
Mochizuki, S., Watanabe, T., Miyake, A., Saito, M. & Furuichi, K. (2000). Cloning, expression, and characterization of ferret 5-HT3 receptor subunit. European Journal of Pharmacology 399, 97–106.Google Scholar
Moorhouse, A. J., Keramidas, A., Zaykin, A., Schofield, P. R. & Barry, P. H. (2002). Single channel analysis of conductance and rectification in cation-selective, mutant glycine receptor channels. Journal of General Physiology 119, 411–425.Google Scholar
Moroni, M. & Bermudez, I. (2006). Stoichiometry and pharmacology of two human alpha4beta2 nicotinic receptor types. Journal of Molecular Neuroscience 30, 95–96.Google Scholar
Moroni, M., Zwart, R., Sher, E., Cassels, B. K. & Bermudez, I. (2006). α4β2 nicotinic receptors with high and low acetylcholine sensitivity: pharmacology, stoichiometry, and sensitivity to long-term exposure to nicotine. Molecular Pharmacology 70, 755–768.Google Scholar
Moss, S. J., Doherty, C. A. & Huganir, R. L. (1992). Identification of the cAMP-dependent protein kinase and protein kinase C phosphorylation sites within the major intracellular domains of the β1, γ2S, and γ2L subunits of the GABAA receptor. Journal of Biological Chemistry 267, 14470–14476.Google Scholar
Moss, S. J., Mcdonald, B. J., Rudhard, Y. & Schoepfer, R. (1996). Phosphorylation of the predicted major intracellular domains of the rat and chick neuronal nicotinic acetylcholine receptor α7 subunit by cAMP-dependent protein kinase. Neuropharmacology 35, 1023–1028.Google Scholar
Mounsey, K. E., Dent, J. A., Holt, D. C., Mccarthy, J., Currie, B. J. & Walton, S. F. (2007). Molecular characterisation of a pH-gated chloride channel from Sarcoptes scabiei. Invertebrate Neuroscience 7, 149–156.Google Scholar
Mu, T. W., Lester, H. A. & Dougherty, D. A. (2003). Different binding orientations for the same agonist at homologous receptors: a lock and key or a simple wedge? Journal of the American Chemical Society 125, 6850–6851.Google Scholar
Muroi, Y., Czajkowski, C. & Jackson, M. B. (2006). Local and global ligand-induced changes in the structure of the GABAA receptor. Biochemistry 45, 7013–7022.Google Scholar
Nakazawa, K., Akiyama, T. & Inoue, K. (1995). Block by 5-hydroxytryptamine of neuronal acetylcholine receptor channels expressed in Xenopus oocytes. Cellular and Molecular Neurobiology 15, 495–500.Google Scholar
Nass, M. M., Lester, H. A. & Krouse, M. E. (1978). Response of acetylcholine receptors to photoisomerizations of bound agonist molecules. Biophysical Journal 24, 135–160.Google Scholar
Navedo, M., Nieves, M., Rojas, L. & Lasalde-Dominicci, J. A. (2004). Tryptophan substitutions reveal the role of nicotinic acetylcholine receptor α-TM3 domain in channel gating: differences between Torpedo and muscle-type AChR. Biochemistry 43, 78–84.CrossRefGoogle ScholarPubMed
Nevin, S. T., Cromer, B. A., Haddrill, J. L., Morton, C. J., Parker, M. W. & Lynch, J. W. (2003). Insights into the structural basis for zinc inhibition of the glycine receptor. Journal of Biological Chemistry 278, 28985–28992.Google Scholar
Ng, H. J., Whittemore, E. R., Tran, M. B., Hogenkamp, D. J., Broide, R. S., Johnstone, T. B., Zheng, L., Stevens, K. E. & Gee, K. W. (2007). Nootropic α7 nicotinic receptor allosteric modulator derived from GABAA receptor modulators. Proceedings of the National Academy of Sciences USA 104, 8059–8064.Google Scholar
Niemeyer, M. I. & Lummis, S. C. (2001). The role of the agonist binding site in Ca(2+) inhibition of the recombinant 5-HT3A receptor. European Journal of Pharmacology 428, 153–161.Google Scholar
Niesler, B., Frank, B., Kapeller, J. & Rappold, G. A. (2003). Cloning, physical mapping and expression analysis of the human 5-HT3 serotonin receptor-like genes HTR3C, HTR3D and HTR3E. Gene 310, 101–111.Google Scholar
Niesler, B., Walstab, J., Combrink, S., Moeller, D., Kapeller, J., Rietdorf, J., Boenisch, H., Goethert, M., Rappold, G. & Bruess, M. (2007). Characterization of the novel human serotonin receptor subunits 5-HT3C, 5- HT3D and 5-HT3E. Molecular Pharmacology 72, 8–17.Google Scholar
Nishizaki, T. & Ikeuchi, Y. (1995). Activation of endogenous protein kinase C enhances currents through α1 and α2 glycine receptor channels. Brain Research 687, 214–216.Google Scholar
Nishizaki, T. & Sumikawa, K. (1998). Effects of PKC and PKA phosphorylation on desensitization of nicotinic acetylcholine receptors. Brain Research 812, 242–245.Google Scholar
Noam, Y., Wadman, W. J. & Van Hooft, J. A. (2008). On the voltage-dependent Ca2+ block of serotonin 5-HT3 receptors: a critical role of intracellular phosphates. Journal of Physiology 586, 3629–3638.Google Scholar
Noda, M., Takahashi, H., Tanabe, T., Toyosato, M., Furutani, Y., Hirose, T., Asai, M., Inayama, S., Miyata, T. & Numa, S. (1982). Primary structure of α-subunit precursor of Torpedo californica acetylcholine receptor deduced from cDNA sequence. Nature 299, 793–797.Google Scholar
Nury, H., Bocquet, N., Le Poupon, C., Raynal, B., Haouz, A., Corringer, P. J. & Delarue, M. 2009. Crystal structure of the extracellular domain of a bacterial ligand-gated ion channel. Journal of Molecular Biology 395, 1114–1127.Google Scholar
O'shea, S. M. & Harrison, N. L. (2000). Arg-274 and Leu-277 of the GABAA receptor α 2 subunit define agonist efficacy and potency. Journal of Biological Chemistry 275, 22764–22768.Google Scholar
Olsen, L., Pettersson, I., Hemmingsen, L., Adolph, H. W. & Jorgensen, F. S. (2004a). Docking and scoring of metallo-beta-lactamases inhibitors. Journal of Computer Aided Molecular Design 18, 287–302.Google Scholar
Olsen, R. W. & Sieghart, W. (2009). GABAA receptors: subtypes provide diversity of function and pharmacology. Neuropharmacology 56, 141–148.Google Scholar
Olsen, R. W., Chang, C. S., Li, G., Hanchar, H. J. & Wallner, M. (2004b). Fishing for allosteric sites on GABAA receptors. Biochemistry and Pharmacology 68, 1675–1684.Google Scholar
Ortiz-Miranda, S. I., Lasalde, J. A., Pappone, P. A. & Mcnamee, M. G. (1997). Mutations in the M4 domain of the Torpedo californica nicotinic acetylcholine receptor alter channel opening and closing. Journal of Membrane Biology 158, 17–30.Google Scholar
Padgett, C. L., Hanek, A. P., Lester, H. A., Dougherty, D. A. & Lummis, S. C. (2007). Unnatural amino acid mutagenesis of the GABAA receptor binding site residues reveals a novel cation–π interaction between GABA and beta 2Tyr97. Journal of Neuroscience 27, 886–892.Google Scholar
Padgett, C. L. & Lummis, S. C. (2008). The F-loop of the GABAA receptor γ2 subunit contributes to benzodiazepine modulation. Journal of Biological Chemistry 283, 2702–2708.Google Scholar
Panicker, S., Cruz, H., Arrabit, C. & Slesinger, P. A. (2002). Evidence for a centrally located gate in the pore of a serotonin-gated ion channel. Journal of Neuroscience 22, 1629–1639.Google Scholar
Panicker, S., Cruz, H., Arrabit, C., Suen, K. F. & Slesinger, P. A. (2004). Minimal structural rearrangement of the cytoplasmic pore during activation of the 5-HT3A receptor. Journal of Biological Chemistry 279, 28149–28158.Google Scholar
Pantoja, R., Rodriguez, E. A., Dibas, M. I., Dougherty, D. A. & Lester, H. A. (2009). Single-molecule imaging of a fluorescent unnatural amino acid incorporated into nicotinic receptors. Biophysical Journal 96, 226–237.Google Scholar
Peters, J. A., Kelley, S. P., Dunlop, J. I., Kirkness, E. F., Hales, T. G. & Lambert, J. J. (2004). The 5-hydroxytryptamine type 3 (5-HT3) receptor reveals a novel determinant of single-channel conductance. Biochemical Society Transactions 32, 547–552.Google Scholar
Peters, J. A., Hales, T. G. & Lambert, J. J. (2005). Molecular determinants of single-channel conductance and ion selectivity in the Cys-loop family: insights from the 5-HT3 receptor. Trends in Pharmacological Science 26, 587–594.Google Scholar
Peters, J. A., Cooper, M. A., Carland, J. E., Livesey, M. R., Hales, T. G. & Lambert, J. J. (2010). Novel structural determinants of single channel conductance and ion selectivity in 5-hydroxytryptamine type 3 and nicotinic acetylcholine receptors. Journal of Physiology 588, 587–595.Google Scholar
Pless, S. A., Dibas, M. I., Lester, H. A. & Lynch, J. W. (2007). Conformational variability of the glycine receptor M2 domain in response to activation by different agonists. Journal of Biological Chemistry 282, 36057–36067.Google Scholar
Pless, S. A. & Lynch, J. W. (2008). Illuminating the structure and function of Cys-loop receptors. Clinical and Experimental Pharmacology and Physiology 35, 1137–1142.Google Scholar
Pless, S. A. & Lynch, J. W. (2009). Distinct conformational changes in activated agonist-bound and agonist-free glycine receptor subunits. Journal of Neurochemistry 108, 1585–1594.Google Scholar
Pless, S. A., Millen, K. S., Hanek, A. P., Lynch, J. W., Lester, H. A., Lummis, S. C. & Dougherty, D. A. (2008). A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue. Journal of Neuroscience 28, 10937–10942.Google Scholar
Price, K. L., Millen, K. S. & Lummis, S. C. (2007). Transducing agonist binding to channel gating involves different interactions in 5-HT3 and GABAC receptors. Journal of Biological Chemistry 282, 25623–25630.Google Scholar
Price, K. L., Bower, K. S., Thompson, A. J., Lester, H. A., Dougherty, D. A. & Lummis, S. C. (2008). A hydrogen bond in loop A is critical for the binding and function of the 5-HT3 receptor. Biochemistry 47, 6370–6377.Google Scholar
Purohit, P., Mitra, A. & Auerbach, A. (2007). A stepwise mechanism for acetylcholine receptor channel gating. Nature 446, 930–933.Google Scholar
Quirk, P. L., Rao, S., Roth, B. L. & Siegel, R. E. (2004). Three putative N-glycosylation sites within the murine 5-HT3A receptor sequence affect plasma membrane targeting, ligand binding, and calcium influx in heterologous mammalian cells. Journal of Neuroscience Research 77, 498–506.Google Scholar
Rajendra, S., Lynch, J. W., Pierce, K. D., French, C. R., Barry, P. H. & Schofield, P. R. (1995). Mutation of an arginine residue in the human glycine receptor transforms β-alanine and taurine from agonists into competitive antagonists. Neuron 14, 169–175.Google Scholar
Ranganathan, R., Cannon, S. C. & Horvitz, H. R. (2000). MOD-1 is a serotonin-gated chloride channel that modulates locomotory behaviour in C. elegans. Nature 408(6811), 470–475.Google Scholar
Rayes, D., De Rosa, M. J., Sine, S. M. & Bouzat, C. (2009). Number and locations of agonist binding sites required to activate homomeric Cys-loop receptors. Journal of Neuroscience 29, 6022–6032.Google Scholar
Reeves, D. C. & Lummis, S. C. (2002). The molecular basis of the structure and function of the 5-HT3 receptor: a model ligand-gated ion channel. Molecular membrane Biology 19, 11–26.Google Scholar
Reeves, D. C., Goren, E. N., Akabas, M. H. & Lummis, S. C. (2001). Structural and electrostatic properties of the 5-HT3 receptor pore revealed by substituted cysteine accessibility mutagenesis. Journal of Biological Chemistry 276, 42035–42042.Google Scholar
Reeves, D. C., Sayed, M. F., Chau, P. L., Price, K. L. & Lummis, S. C. (2003). Prediction of 5-HT3 receptor agonist-binding residues using homology modeling. Biophysical Journal 84, 2338–2344.Google Scholar
Roe, D. C. & Kuntz, I. D. (1995). BUILDER v.2: improving the chemistry of a de novo design strategy. Journal of Computer Aided Molecular Design 9, 269–282.Google Scholar
Romanelli, M. N., Gratteri, P., Guandalini, L., Martini, E., Bonaccini, C. & Gualtieri, F. (2007). Central nicotinic receptors: structure, function, ligands, and therapeutic potential. ChemMedChem 2, 746–767.Google Scholar
Rovira, J. C., Ballesta, J. J., Vicente-Agullo, F., Campos-Caro, A., Criado, M., Sala, F. & Sala, S. (1998). A residue in the middle of the M2–M3 loop of the β4 subunit specifically affects gating of neuronal nicotinic receptors. FEBS Letters 433, 89–92.Google Scholar
Rovira, J. C., Vicente-Agullo, F., Campos-Caro, A., Criado, M., Sala, F., Sala, S. & Ballesta, J. J. (1999). Gating of α3β4 neuronal nicotinic receptor can be controlled by the loop M2-M3 of both α3 and β4 subunits. Pflugers Archives 439, 86–92.Google Scholar
Rudolph, U., Crestani, F. & Mohler, H. (2001). GABAA receptor subtypes: dissecting their pharmacological functions. Trends in Pharmacological Science 22, 188–194.Google Scholar
Ruiz-Gomez, A., Vaello, M. L., Valdivieso, F. & Mayor, F. Jr. ( 1991). Phosphorylation of the 48-kDa subunit of the glycine receptor by protein kinase C. Journal of Biological Chemistry 266, 559–566.Google Scholar
Rundstrom, N., Schmieden, V., Betz, H., Bormann, J. & Langosch, D. (1994). Cyanotriphenylborate: subtype-specific blocker of glycine receptor chloride channels. Proceedings of the National Academy of Sciences USA 91, 8950–8954.Google Scholar
Sali, A. & Blundell, T. L. (1993). Comparative protein modelling by satisfaction of spatial restraints. Journal of Molecular Biology 234, 779–815.Google Scholar
Sarto-Jackson, I. & Sieghart, W. (2008). Assembly of GABAA receptors (Review). Molecular Membrane Biology 25, 302–310.Google Scholar
Saul, B., Kuner, T., Sobetzko, D., Brune, W., Hanefeld, F., Meinck, H. M. & Becker, C. M. (1999). Novel GLRA1 missense mutation (P250T) in dominant hyperekplexia defines an intracellular determinant of glycine receptor channel gating. Journal of Neuroscience 19, 869–877.Google Scholar
Schapira, M., Abagyan, R. & Totrov, M. (2002). Structural model of nicotinic acetylcholine receptor isotypes bound to acetylcholine and nicotine. BMC Structural Biology 2, 1.Google Scholar
Schärer, K., Morgenthaler, M., Paulini, R., Obst-Sander, U., Banner, D. W., Schlatter, D., Benz, J., Stihle, M. & Diederich, F. (2005). Quantification of cation–π interactions in protein–ligand complexes: crystal-structure analysis of factor Xa bound to a quaternary ammonium ion ligand. Angewandte Chemie International Edition: English 44(28), 4400–4404.Google Scholar
Schmidt, A. W. & Peroutka, S. J. (1989). Three-dimensional steric molecular modeling of the 5-hydroxytryptamine3 receptor pharmacophore. Molecular Pharmacology 36, 505–511.Google Scholar
Schofield, C. M., Jenkins, A. & Harrison, N. L. (2003). A highly conserved aspartic acid residue in the signature disulfide loop of the α1 subunit is a determinant of gating in the glycine receptor. Journal of Biological Chemistry 278, 34079–34083.Google Scholar
Schreiter, C., Hovius, R., Costioli, M., Pick, H., Kellenberger, S., Schild, L. & Vogel, H. (2003). Characterization of the ligand-binding site of the serotonin 5-HTα receptor: the role of glutamate residues 97, 224 and 235. Journal of Biological Chemistry 278, 22709–22716.Google Scholar
Schulte, M. K., Hill, R. A., Bikadi, Z., Maksay, G., Parihar, H. S., Joshi, P. & Suryanarayanan, A. (2006). The structural basis of ligand interactions in the 5-HT3 receptor binding site. In Biological and Biophysical Aspects of Ligand-Gated Ion Channel Receptor Superfamilies (Ed. Arias, H. R.), pp. 127–153. Kerala, India: Research Signpost.Google Scholar
Sedelnikova, A., Smith, C. D., Zakharkin, S. O., Davis, D., Weiss, D. S. & Chang, Y. (2005). Mapping the rho1 GABAC receptor agonist binding pocket. Constructing a complete model. Journal of Biological Chemistry 280, 1535–1542.Google Scholar
Sedelnikova, A. & Weiss, D. S. (2002). Phosphorylation of the recombinant rho1 GABA receptor. International Journal of Developmental Neuroscience 20, 237–246.Google Scholar
Sessoms-Sikes, J. S., Hamilton, M. E., Liu, L. X., Lovinger, D. M. & Machu, T. K. (2003). A mutation in transmembrane domain II of the 5-hydroxytryptamine3A receptor stabilizes channel opening and alters alcohol modulatory actions. Journal of Pharmacology and Experimental Therapeutics 306, 595–604.Google Scholar
Shan, Q., Haddrill, J. L. & Lynch, J. W. (2001). A single β subunit M2 domain residue controls the picrotoxin sensitivity of αβ heteromeric glycine receptor chloride channels. Journal of Neurochemistry 76, 1109–1120.Google Scholar
Shan, Q., Haddrill, J. L. & Lynch, J. W. (2002). Comparative surface accessibility of a pore-lining threonine residue (T6′) in the glycine and GABAA receptors. Journal of Biological Chemistry 277, 44845–44853.Google Scholar
Sheridan, R. E. & Lester, H. A. (1982). Functional stoichiometry at the nicotinic receptor. The photon cross section for phase 1 corresponds to two bis-Q molecules per channel. Journal of General Physiology 80, 499–515.Google Scholar
Shi, J., Blundell, T. L. & Mizuguchi, K. (2001). FUGUE: sequence-structure homology recognition using environment-specific substitution tables and structure-dependent gap penalties. Journal of Molecular Biology 310, 243–257.Google Scholar
Sigel, E. (2002). Mapping of the benzodiazepine recognition site on GABAA receptors. Current Topics in Medicinal Chemistry 2, 833–839.Google Scholar
Sigel, E. & Buhr, A. (1997). The benzodiazepine binding site of GABAA receptors. Trends in Pharmacological Science 18, 425–429.Google Scholar
Sigel, E., Buhr, A. & Baur, R. (1999). Role of the conserved lysine residue in the middle of the predicted extracellular loop between M2 and M3 in the GABAA receptor. Journal of Neurochemistry 73, 1758–1764.Google Scholar
Sine, S. M., Wang, H. L., Hansen, S. & Taylor, P. (2010). On the origin of ion selectivity in the Cys-loop receptor family. Journal of Molecular Neuroscience 40, 70–76.Google Scholar
Slimko, E. M. & Lester, H. A. (2003). Codon optimization of Caenorhabditis elegans GluCl ion channel genes for mammalian cells dramatically improves expression levels. Journal of Neuroscience Methods 124, 75–81.Google Scholar
Slimko, E. M., Mckinney, S., Anderson, D. J., Davidson, N. & Lester, H. A. (2002). Selective electrical silencing of mammalian neurons in vitro by the use of invertebrate ligand-gated chloride channels. Journal of Neuroscience 22, 7373–7379.Google Scholar
Smart, O. S., Goodfellow, J. M. & Wallace, B. A. (1993). The pore dimensions of gramicidin A. Biophysical Journal 65, 2455–2460.Google Scholar
Spier, A. D. & Lummis, S. C. (2000). The role of tryptophan residues in the 5-Hydroxytryptamine3 receptor ligand binding domain. Journal of Biological Chemistry 275, 5620–5625.Google Scholar
Spitzmaul, G., Corradi, J. & Bouzat, C. (2004). Mechanistic contributions of residues in the M1 transmembrane domain of the nicotinic receptor to channel gating. Molecular Membrane Biology 21, 39–50.Google Scholar
Sullivan, N. L., Thompson, A. J., Price, K. & Lummis, S. C. R. (2006). Defining the roles of Asn-128, Glu-129 and Phe-130 in loop A of the 5-HT3 receptor. Molecular Membrane Biology 23, 1–10.Google Scholar
Sun, H., Hu, X. Q., Moradel, E. M., Weight, F. F. & Zhang, L. (2003). Modulation of 5-HT3 receptor-mediated response and trafficking by activation of protein kinase C. Journal of Biological Chemistry 278, 34150–34157.Google Scholar
Sunesen, M., De Carvalho, L. P., Dufresne, V., Grailhe, R., Savatier-Duclert, N., Gibor, G., Peretz, A., Attali, B., Changeux, J. P. & Paas, Y. (2006). Mechanism of Cl- selection by a glutamate-gated chloride (GluCl) receptor revealed through mutations in the selectivity filter. Journal of Biological Chemistry 281, 14875–14881.Google Scholar
Suryanarayanan, A., Joshi, P. R., Bikadi, Z., Mani, M., Kulkarni, T. R., Gaines, C. & Schulte, M. K. (2005). The loop C region of the murine 5-HT3A receptor contributes to the differential actions of 5-hydroxytryptamine and m-chlorophenylbiguanide. Biochemistry 44, 9140–9149.Google Scholar
Suzuki, T., Koyama, H., Sugimoto, M., Uchida, I. & Mashimo, T. (2002). The diverse actions of volatile and gaseous anesthetics on human-cloned 5-hydroxytryptamine3 receptors expressed in Xenopus oocytes. Anesthesiology 96, 699–704.Google Scholar
Tamamizu, S., Lee, Y., Hung, B., Mcnamee, M. G. & Lasalde-Dominicci, J. A. (1999). Alteration in ion channel function of mouse nicotinic acetylcholine receptor by mutations in the M4 transmembrane domain. Journal of Membrane Biology 170, 157–164.Google Scholar
Tamamizu, S., Guzman, G. R., Santiago, J., Rojas, L. V., Mcnamee, M. G. & Lasalde-Dominicci, J. A. (2000). Functional effects of periodic tryptophan substitutions in the α M4 transmembrane domain of the Torpedo californica nicotinic acetylcholine receptor. Biochemistry 39, 4666–4673.Google Scholar
Tan, K. R., Baur, R., Gonthier, A., Goeldner, M. & Sigel, E. (2007). Two neighboring residues of loop A of the alpha1 subunit point towards the benzodiazepine binding site of GABAA receptors. FEBS Letters 581, 4718–4722.Google Scholar
Tapia, L., Kuryatov, A. & Lindstrom, J. (2007). Ca2+ permeability of the (α4)3(β2)2 stoichiometry greatly exceeds that of (α4)2(β2)3 human acetylcholine receptors. Molecular Pharmacology 71, 769–776.Google Scholar
Teissere, J. A. & Czajkowski, C. (2001). A β-strand in the γ2 subunit lines the benzodiazepine binding site of the GABAA receptor: structural rearrangements detected during channel gating. Journal of Neuroscience 21, 4977–4986.Google Scholar
Thompson, A. J. & Lummis, S. C. (2003). A single ring of charged amino acids at one end of the pore can control ion selectivity in the 5-HT3 receptor. British Journal of Pharmacology 140(2), 359–365.Google Scholar
Thompson, A. J. & Lummis, S. C. (2006). 5-HT3 receptors. Current Pharmaceutical Design 12, 3615–3630.Google Scholar
Thompson, A. J. & Lummis, S. C. (2008a). Calcium modulation of 5-HT3 receptor binding and function. Neuropharmacology 56, 285–291.Google Scholar
Thompson, A. J. & Lummis, S. C. R. (2008b). Antimalarial drugs inhibit human 5-HT3 and GABAA, but not GABAC receptors. British Journal of Pharmacology 153, 1686–1696.Google Scholar
Thompson, A. J., Price, K. L., Reeves, D. C., Chan, S. L., Chau, P. L. & Lummis, S. C. (2005). Locating an antagonist in the 5-HT3 receptor binding site using modeling and radioligand binding. Journal of Biological Chemistry 280, 20476–20482.Google Scholar
Thompson, A. J., Chau, P. L., Chan, S. L. & Lummis, S. C. (2006a). Unbinding pathways of an agonist and an antagonist from the 5-HT3 receptor. Biophysical Journal 90, 1979–1991.Google Scholar
Thompson, A. J., Padgett, C. L. & Lummis, S. C. (2006b). Mutagenesis and molecular modeling reveal the importance of the 5-HT3 receptor F-loop. Journal of Biological Chemistry 281, 16576–16582.Google Scholar
Thompson, A. J., Lochner, M. & Lummis, S. C. (2008). Loop B is a major structural component of the 5-HT3 receptor. Biophysical Journal 95, 5728–5736.Google Scholar
Tikhonov, D. B., Mellor, I. R. & Usherwood, P. N. (2004). Modeling noncompetitive antagonism of a nicotinic acetylcholine receptor. Biophysical Journal 87, 159–170.Google Scholar
Trudell, J. R. & Bertaccini, E. (2004). Comparative modeling of a GABAA alpha1 receptor using three crystal structures as templates. Journal of Molecular Graphics and Modelling 23, 39–49.Google Scholar
Tzvetkov, M. V., Meineke, C., Oetjen, E., Hirsch-Ernst, K. & Brockmoller, J. (2007). Tissue-specific alternative promoters of the serotonin receptor gene HTR3B in human brain and intestine. Gene 386, 52–62.Google Scholar
Ulbrich, M. H. & Isacoff, E. Y. (2007). Subunit counting in membrane-bound proteins. Nature Methods 4, 319–321.Google Scholar
Unwin, N. (1993). Nicotinic acetylcholine receptor at 9 Å resolution. Journal of Molecular Biology 229, 1101–1124.Google Scholar
Unwin, N. (1995). Acetylcholine receptor channel imaged in the open state. Nature 373, 37–43.Google Scholar
Unwin, N. (2000). The Croonian Lecture 2000. Nicotinic acetylcholine receptor and the structural basis of fast synaptic transmission. Philosophical Transactions of the Royal Society of London B: Biological Science 355, 1813–1829.Google Scholar
Unwin, N. (2005). Refined structure of the nicotinic acetylcholine receptor at 4 Å resolution. Journal of Molecular Biology 346, 967–989.Google Scholar
Unwin, N., Miyazawa, A., Li, J. & Fujiyoshi, Y. (2002). Activation of the nicotinic acetylcholine receptor involves a switch in conformation of the alpha subunits. Journal of Molecular Biology 319, 1165–1176.Google Scholar
Urban, B. W., Bleckwenn, M. & Barann, M. (2006). Interactions of anesthetics with their targets: non-specific, specific or both? Pharmacology and Therapeutics 111, 729–770.Google Scholar
Vaello, M. L., Ruiz-Gomez, A., Lerma, J. & Mayor, F. Jr. ( 1994). Modulation of inhibitory glycine receptors by phosphorylation by protein kinase C and cAMP-dependent protein kinase. Journal of Biological Chemistry 269, 2002–2008.Google Scholar
Van Hooft, J. A. & Vijverberg, H. P. (1995). Phosphorylation controls conductance of 5-HT3 receptor ligand-gated ion channels. Receptors Channels 3, 7–12.Google Scholar
Van Hooft, J. A. & Wadman, W. J. (2003). Ca2+ ions block and permeate serotonin 5-HT3 receptor channels in rat hippocampal interneurons. Journal pf Neurophysiology 89, 1864–1869.Google Scholar
Vassilatis, D. K., Arena, J. P., Plasterk, R. H., Wilkinson, H. A., Schaeffer, J. M., Cully, D. F. & Van Der Ploeg, L. H. (1997). Genetic and biochemical evidence for a novel avermectin-sensitive chloride channel in Caenorhabditis elegans. Isolation and characterization. Journal of Biological Chemistry 272, 33167–33174.Google Scholar
Venkataraman, P., Joshi, P., Venkatachalan, S. P., Muthalagi, M., Parihar, H. S., Kirschbaum, K. S. & Schulte, M. K. (2002a). Functional group interactions of a 5-HT3R antagonist. BMC Biochemistry 3, 16.Google Scholar
Venkataraman, P., Venkatachalan, S. P., Joshi, P. R., Muthalagi, M. & Schulte, M. K. (2002b). Identification of critical residues in loop E in the 5-HT3ASR binding site. BMC Biochemistry 3, 15.Google Scholar
Vernekar, S. K., Hallaq, H. Y., Clarkson, G., Thompson, A. J., Silvestri, L., Lummis, S. C. & Lochner, M. 2010. Toward biophysical probes for the 5-HT3 receptor: structure-activity relationship study of granisetron derivatives. Journal of Medicinal Chemistry 53, 2324–2328.Google Scholar
Vernino, S., Amador, M., Luetje, C. W., Patrick, J. & Dani, J. A. (1992). Calcium modulation and high calcium permeability of neuronal nicotinic acetylcholine receptors. Neuron 8, 127–134.Google Scholar
Villmann, C., Oertel, J., Ma-Hogemeier, Z. L., Hollmann, M., Sprengel, R., Becker, K., Breitinger, H. G. & Becker, C. M. (2009). Functional complementation of Glra1(spd-ot), a glycine receptor subunit mutant, by independently expressed C-terminal domains. Journal of Neuroscience 29, 2440–5242.Google Scholar
Violet, J. M., Downie, D. L., Nakisa, R. C., Lieb, W. R. & Franks, N. P. (1997). Differential sensitivities of mammalian neuronal and muscle nicotinic acetylcholine receptors to general anesthetics. Anesthesiology 86, 866–874.Google Scholar
Wang, M. D. & Axelrod, D. (1994). Time-lapse total internal reflection fluorescence video of acetylcholine receptor cluster formation on myotubes. Developmental Dynamics 201, 29–40.Google Scholar
Wang, F. & Imoto, K. (1992). Pore size and negative charge as structural determinants of permeability in the Torpedo nicotinic acetylcholine receptor channel. Proceedings of the Royal Society of London B: Biological Sciences 250, 11–17.Google Scholar
Wang, H. L., Milone, M., Ohno, K., Shen, X. M., Tsujino, A., Batocchi, A. P., Tonali, P., Brengman, J., Engel, A. G. & Sine, S. M. (1999). Acetylcholine receptor M3 domain: stereochemical and volume contributions to channel gating. Nature Neuroscience 2, 226–233.Google Scholar
Wang, J., Lester, H. A. & Dougherty, D. A. (2007). Establishing an ion pair interaction in the homomeric ρ1 GABAA receptor that contributes to the gating pathway. Journal of Biological Chemistry 282, 26210–26216.Google Scholar
Webb, T. I. & Lynch, J. W. (2007). Molecular pharmacology of the glycine receptor chloride channel. Current Pharmaceutical Design 13, 2350–2367.Google Scholar
Wecker, L., Guo, X., Rycerz, A. M. & Edwards, S. C. (2001). Cyclic AMP-dependent protein kinase (PKA) and protein kinase C phosphorylate sites in the amino acid sequence corresponding to the M3/M4 cytoplasmic domain of α4 neuronal nicotinic receptor subunits. Journal of Neurochemistry 76, 711–720.Google Scholar
Werner, P., Kawashima, E., Reid, J., Hussy, N., Lundstrom, K., Buell, G., Humbert, Y. & Jones, K. A. (1994). Organization of the mouse 5-HT3 receptor gene and functional expression of two splice variants. Brain Research and Molecular Brain Research 26, 233–241.Google Scholar
Williams, D. B. & Akabas, M. H. (1999). GABA increases the water accessibility of M3 membrane-spanning segment residues in GABAA receptors. Biophysical Journal 77, 2563–2574.Google Scholar
Wilson, G. G. & Karlin, A. (1998). The location of the gate in the acetylcholine receptor channel. Neuron 20, 1269–1281.Google Scholar
Wilson, G. & Karlin, A. (2001). Acetylcholine receptor channel structure in the resting, open, and desensitized states probed with the substituted-cysteine-accessibility method. Proceedings of the National Academy of Sciences USA 98, 1241–1248.Google Scholar
Wilson, G. G., Pascual, J. M., Brooijmans, N., Murray, D. & Karlin, A. (2000). The intrinsic electrostatic potential and the intermediate ring of charge in the acetylcholine receptor channel. Journal of General Physiology 115, 93–106.Google Scholar
Wotring, V. E. & Weiss, D. S. (2008). Charge scan reveals an extended region at the intracellular end of the GABA receptor pore that can influence ion selectivity. Journal of General Physiology 131(1), 87–97.Google Scholar
Wotring, V. E., Miller, T. S. & Weiss, D. S. (2003). Mutations at the GABA receptor selectivity filter: a possible role for effective charges. Journal of Physiology 548, 527–540.Google Scholar
Wu, D. F., Othman, N. A., Sharp, D., Mahendra, A., Deeb, T. Z. & Hales, T. G. (2010). A conserved cysteine residue in the third transmembrane domain is essential for homomeric 5-HT3 receptor function. Journal of Physiology 588, 603–616.Google Scholar
Xiu, X., Hanek, A. P., Wang, J., Lester, H. A. & Dougherty, D. A. (2005). A unified view of the role of electrostatic interactions in modulating the gating of Cys loop receptors. Journal of Biological Chemistry 280, 41655–41666.Google Scholar
Xiu, X., Puskar, N. L., Shanata, J. A., Lester, H. A. & Dougherty, D. A. (2009). Nicotine binding to brain receptors requires a strong cation–π interaction. Nature 458, 534–537.Google Scholar
Xu, M. & Akabas, M. H. (1993). Amino acids lining the channel of the GABAA receptor identified by cysteine substitution. Journal of Biological Chemistry 268, 21505–21508.Google Scholar
Xu, M. & Akabas, M. H. (1996). Identification of channel-lining residues in the M2 membrane-spanning segment of the GABAA receptor α1 subunit. Journal of General Physiology 107, 195–205.Google Scholar
Xu, M., Covey, D. F. & Akabas, M. H. (1995). Interaction of picrotoxin with GABAA receptor channel-lining residues probed in cysteine mutants. Biophysical Journal 69, 1858–1867.Google Scholar
Yakel, J. L. (2010). Gating of nicotinic ACh receptors: latest insights into ligand binding and function. Journal of Physiology 588, 597–602.Google Scholar
Yakel, J. L., Shao, X. M. & Jackson, M. B. (1990). The selectivity of the channel coupled to the 5-HT3 receptor. Brain Research 533, 46–52.Google Scholar
Yamakura, T., Bertaccini, E., Trudell, J. R. & Harris, R. A. (2001). Anesthetics and ion channels: molecular models and sites of action. Annual Review in Pharmacology and Toxicology 41, 23–51.Google Scholar
Yan, D., Schulte, M. K., Bloom, K. E. & White, M. M. (1999). Structural features of the ligand-binding domain of the serotonin 5HT3 receptor. Journal of Biological Chemistry 274, 5537–5541.Google Scholar
Yan, D. & White, M. M. (2005). Spatial orientation of the antagonist granisetron in the ligand-binding site of the 5-HT3 receptor. Molecular Pharmacology 68, 365–371.Google Scholar
Yang, J. (1990). Ion permeation through 5-hydroxytryptamine-gated channels in neuroblastoma N18 cells. Journal of General Physiology 96, 1177–1198.Google Scholar
Yu, X. M. & Hall, Z. W. (1994). A sequence in the main cytoplasmic loop of the alpha subunit is required for assembly of mouse muscle nicotinic acetylcholine receptor. Neuron 13, 247–255.Google Scholar
Zhang, H. & Karlin, A. (1997). Identification of acetylcholine receptor channel-lining residues in the M1 segment of the beta-subunit. Biochemistry 36, 15856–15864.Google Scholar
Zhang, H. & Karlin, A. (1998). Contribution of the beta subunit M2 segment to the ion-conducting pathway of the acetylcholine receptor. Biochemistry 37, 7952–7964.Google Scholar
Zhang, L., Oz, M., Stewart, R. R., Peoples, R. W. & Weight, F. F. (1997). Volatile general anaesthetic actions on recombinant nACh α7, 5-HT3 and chimeric nACh α7-5-HT3 receptors expressed in Xenopus oocytes. British Journal of Pharmacology 120, 353–355.Google Scholar
Zhang, D., Gullingsrud, J. & Mccammon, J. A. (2006). Potentials of mean force for acetylcholine unbinding from the α7 nicotinic acetylcholine receptor ligand-binding domain. Journal of the American Chemical Society 128, 3019–3026.Google Scholar
Zheng, Y., Hirschberg, B., Yuan, J., Wang, A. P., Hunt, D. C., Ludmerer, S. W., Schmatz, D. M. & Cully, D. F. (2002). Identification of two novel Drosophila melanogaster histamine-gated chloride channel subunits expressed in the eye. Journal of Biological Chemistry 277, 2000–2005.Google Scholar
Zheng, J. & Zagotta, W. N. (2003). Patch-clamp recording of conformational rearrangements of ion channels. Science Signalling: Signal Transduction Knowledge Environment 176, PL7.Google Scholar
Zuo, Y., Kuryatov, A., Lindstrom, J. M., Yeh, J. Z. & Narahashi, T. (2002). Alcohol modulation of neuronal nicotinic acetylcholine receptors is alpha subunit dependent. Alcoholism: Clinical and Experimental Research 26, 779–784.Google Scholar