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The physiology and pharmacology of neuromuscular transmission in the nematode parasite, Ascaris suum

Published online by Cambridge University Press:  06 April 2009

R. J. Martin
Affiliation:
Department of Pre-clinical Veterinary Sciences, R.(D).S.V.S. University of Edinburgh, Edinburgh EH9 1QH
A. J. Pennington
Affiliation:
Department of Pre-clinical Veterinary Sciences, R.(D).S.V.S. University of Edinburgh, Edinburgh EH9 1QH
A. H. Duittoz
Affiliation:
Department of Pre-clinical Veterinary Sciences, R.(D).S.V.S. University of Edinburgh, Edinburgh EH9 1QH
S. Robertson
Affiliation:
Department of Pre-clinical Veterinary Sciences, R.(D).S.V.S. University of Edinburgh, Edinburgh EH9 1QH
J. R. Kusel
Affiliation:
Department of Biochemistry, University of Glasgow, Glasgow G12 8QQ

Extract

The organization of Ascaris motoneurones and nervous system is summarized. There is an anterior nerve ring and associated ganglia, main dorsal and ventral nerve cords which run longitudinally, and a small set of posterior ganglia. Cell bodies of motoneurones are found in the ventral nerve cord and occur in 5 repeating ‘segments’; each contains 11 motoneurones. Seven morphological types of excitatory or inhibitory motoneurone are recognized.

Each Ascaris somatic muscle cell is composed of the contractile spindle; the bag region, containing the nucleus; the arm; and the syncytial region, the location of neuromuscular junctions. The resting membrane potential of muscle is approximately — 30 mV and shows regular depolarizing, Ca-dependent ‘spike potentials’ superimposed on smaller Na+- and Ca2+-dependent ‘slow waves’ and even slower ‘modulation waves’. The membrane shows high Cl- permeability. Adjacent cells are electrically coupled so that electrical activity in the cells is synchronized. Acetylcholine (ACh) and γ-aminobutyric acid (GABA) affect the electrical activity. Bath-applied ACh increases membrane cation conductance, depolarizes the cells, alters the frequency and amplitude of spike potentials and produces contraction. Bath-applied GABA increases Cl- conductance, decreases spike activity and causes hyperpolarization and muscle relaxation.

The extra-synaptic ACh receptors on the bag region of Ascaris muscle can be regarded as a separate subtype of nicotinic receptor. ACh and anthelmintic agonists (pyrantel, morantel, levamisole) produce a dose-dependent increase in cation conductance and membrane depolarization which is blocked by tubocurarine, mecamylamine but not by hexamethonium. The potency, of GABA agonists, with the exception of sulphonic acid derivatives, correlates with the vertebrate GABAa receptor. The potency of antagonists does not. Thus, bicuculline, securinine, pitrazepine, SR95531 and RU5135 are potent vertebrate GABAa antagonists but have little effect on GABA receptors. The potency order of the arylaminopyridazine GABA antagonists: SR95103, SR95132, SR42666, SR95133, SR95531, SR42627 and SR42640 at the Ascaris GABA receptors contrasts with that at vertebrate GABAa receptors. It has been suggested that the receptor is referred to as a GABAn receptor.

Patch-clamp studies show that ACh activates a non-selective cation channel which has a main conductance of 40–50pS and apparent mean open time of 1·3 ms; a smaller channel of 20–30 pS with a similar open-time is also activated. Pyrantel and levamisole also produce openings with similar conductances and open-times. GABA activates a Cl- channel with a main state conductance of 22 pS and an apparent mean open duration of 32 ms; conductance states of 10 and 15 pS are also seen. Piperazine similarly activates this channel but the mean open-time is shorter (14 ms). Ivermectin in high doses, is an antagonist which reduces the GABA channel conductance and Popen; it does, however, open ‘small’ Cl- channels when applied to the outside surface of membrane. These channels have a conductance of 9–15 pS and very long open times (> 100 mS). 5-HT does not have a direct effect on membrane potential or conductance but acts on cAMP levels and glycogen metabolism. Dopamine, octopamine and AF1 may act as neurotransmitters or neuromodulators.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1991

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References

Aceves, J., Erliji, D. & Martinez-Marnon, R. (1970). The mechanism of the paralysing action of tetramisole on Ascaris somatic muscle. British Journal of Pharmacology 38, 332–44.CrossRefGoogle ScholarPubMed
Angstadt, J. D., Donmoyer, J. E. & Stretton, A. O. W. (1989). Retrovesicular ganglion of the nematode Ascaris. Journal of Comparative Neurology 284, 374–88.CrossRefGoogle ScholarPubMed
Ariens, E. J., Beld, A. D., Miranda, J. F. R. & Simonis, A. M. (1979). The Pharmacon-Receptor-Effector concept. In The Receptors vol. 1 (ed. O'Brien, R. D.), New York: Plenum.Google Scholar
Aubry, M. L., Cowell, P., Davey, M. J. & Shevde, S. (1970). Aspects of the pharmacology of new anthelmintics: pyrantel. British Journal of Pharmacology 38, 332–44.CrossRefGoogle ScholarPubMed
Baldwin, E. & Moyle, v. (1949). A contribution to the physiology and pharmacology of Ascaris lumbricoides from the pig. British Journal of Pharmacology 4, 145–52.Google Scholar
Brading, A. F. & Caldwell, P. C. (1971). The resting membrane potential of the somatic muscle cells of Ascaris lumbricoides. Journal of Physiology 217, 605–24.Google Scholar
Bueding, E. (1952). Acetylcholinesterase activity of Schistosoma mansoni. British Journal of Pharmacology 7, 563–6.Google ScholarPubMed
Caldwell, P. C. (1974). Possible mechanisms for linkage of membrane potentials to metabolism by electrogenic transport processes with special reference to Ascaris muscle. Bioenergetics 4, 201–9.CrossRefGoogle Scholar
Caldwell, P. C. & Ellory, J. C. (1968). Ion movement in the somatic muscle cells of Ascaris lumbricoides. Journal of Physiology 197, 7576P.Google ScholarPubMed
Baillon, P.Cappe de (1911). Etude sur les fibres musculaires d'Ascaris. I. Fibres pariétales. Cellule 27, 165211.Google Scholar
Chambon, J. P., Feltz, P., Heaulme, M., Restle, S., Schliechter, R., Bizière, K. & Wermuth, C. G. (1985). Synthesis of SR95103 an arylaminopyridazine derivative of GABA. Proceedings of the National Academy of Sciences USA 82, 1832–6.Google Scholar
Chaudhuri, J. & Donahue, M. J. (1989). Serotonin receptors in the tissues of adult Ascaris suum. Molecular and Biochemical Parasitology 35, 191–8.CrossRefGoogle ScholarPubMed
Coles, G. C., East, J. M. & Jenkins, S. N. (1975). The mechanism of action of the anthelmintic levamisole. General Pharmacology 6, 309–13.CrossRefGoogle Scholar
Colquhoun, L., Holden-Dye, L. & Walker, R. J. (1989). 5-Nitro-2-(3-phenylpropylamino) benzoic acid, (5-NPB), is a non-competitive antagonist at the Ascaris GABA receptor. British Journal of Pharmacology 97, 369P.Google Scholar
Colquhoun, L., Holden-Dye, L. & Walker, R. J. (1990). The pharmacology of cholinoceptors on the somatic muscle cells of the parasitic nematode Ascaris suum. British Journal of Pharmacology 99, 253P.Google Scholar
Cowden, C., Stretton, A. O. W. & Davis, R. E. (1989). AF1, a sequenced bioactive neuropeptide isolated from the nematode Ascaris suum. Neuron 2, 1465–73.CrossRefGoogle ScholarPubMed
Davenport, T. R. B., Lee, D. L. & Isaac, R. E. (1988). Immunocytochemical demonstration of a neuropeptide in Ascaris suum (Nematoda) using antiserum to FMRF-amide. Parasitology 97, 81–8.Google Scholar
Davis, R. E. & Stretton, A. O. W. (1989 a). Passive membrane properties of motoneurons and their role in long-distance signalling in the nematode Ascaris. Journal of Neuroscience 9, 403–14.CrossRefGoogle ScholarPubMed
Davis, R. E. & Stretton, A. O. W. (1989 b). Signalling properties of Ascaris motoneurons: graded active responses, graded synaptic transmission, and tonic transmitter release. Journal of Neuroscience 9, 415–25.CrossRefGoogle ScholarPubMed
Bell, J. T.de (1965). A long look at neuromuscular junctions in nematodes. Quarterly Review of Biology 40, (3) 233–51.Google Scholar
Bell, J. T.de, Castillo, J.Del & Sanchez, V. (1963). Electrophysiology of the somatic muscle cells of Ascaris lumbricoides. Journal of Cellular and Comparative Physiology 62, 159–77.Google Scholar
Mello, W. C.de & Maldonado, H. (1985). Synaptic inhibition and cell communication; impairment of cell-to-cell coupling produced by gamma-aminobutyric acid (GABA) in the somatic musculature of Ascaris lumbricoides. Cellular Biology International Report 9, 803–13.Google ScholarPubMed
Castillo, J.del, Mello, W. C.de & Morales, T. (1963). The physiological role of acetylcholine in the neuromuscular system of Ascaris lumbricoides. Archives internationales de physiologie et de biochimie 71, 741–57.CrossRefGoogle Scholar
Castillo, J.del, Mello, W. C.de & Morales, T. (1964a). Influence of some ions on the membrane potential of Ascaris muscle. Journal of General Physiology 48, 129–40.Google Scholar
Castillo, J.del, Mello, W. C.de & Morales, T. (1964 b). Inhibitory action of γ-aminobutyric acid (GABA) on Ascaris muscle. Experientia 20, 141–3.Google Scholar
Castillo, J.del, Mello, W. C.de & Morales, T. (1964 c). Mechanism of the paralysing action of piperazine on Ascaris muscle. British Journal of Pharmacology 22, 463–77.Google Scholar
Castillo, J.del, Mello, W. C.de & Morales, T. (1967). The initiation of action potentials in the somatic musculature of Ascaris lumbricoides. Journal of Experimental Biology 46, 263–79.Google Scholar
Castillo, J.del, Rivera, A., Solorzano, S. & Serrato, J. (1989). Some aspects of the neuromuscular system of Ascaris. Quarterly Journal of Experimental Physiology 74, 1071–89.Google Scholar
Donahue, M. J., Masaracchia, R. A. & Harris, B. G. (1983). The role of cyclic AMP-mediated regulation of glycogen metabolism in levamisole-perfused Ascaris muscle. Molecular Pharmacology 23, 378–83.Google Scholar
Donahue, M. J., Yacoub, N. J. & Harris, B. J. (1982). Correlation of muscle activity with glycogen metabolism in muscle of Ascaris suum. American Journal of Physiology 242, R514–R521.Google Scholar
Donahue, M. J., Yacoub, N. J., Michinoff, C. A., Masaracchia, R. A. & Harris, B. G. (1981). Serotonin (5-hydroxytryptamine): a possible regulator of glycogenolysis in perfused muscle segmens of Ascaris suum. Biophysics and Biochemical Research Communications 101, 112–17.CrossRefGoogle Scholar
Duittoz, A. H. & Martin, R. J. (1989). SR95103 acts as a GABA antagonist in Ascaris suum muscle. British Journal of Pharmacology 97, 490P.Google Scholar
Duittoz, A. H. & Martin, R. J. (1990 a). Effects of the arylaminopyridazine-GABA derivatives, SR95103 and SR95531 on the Ascaris muscle GABA receptor: the relative potency of the antagonists in Ascaris is different to that at vertebrate GABAa receptors. Journal of Comparative Biochemistry and Physiology (In Press).Google Scholar
Duittoz, A. H. & Martin, R. J. (1990 b). Effects of SR95103 on GABA-activated single-channel currents from Ascaris suum muscle. Journal of Comparative Biochemistry and Physiology (In Press).Google Scholar
Eyre, P. (1970). Some pharmacodynamic effects of the nematocides: methyridine, tetramisole and pyrantel. Journal of Pharmacy and Pharmacology 22, 2636.Google Scholar
Goldschmidt, R. (1908). Das Nervensystem von Ascaris lumbricoides und Megalocephala. Ein Versuch, in den Aufbau eines einfachen Nervensystems einzudringen, Zweiter Teil. Zeitschrift für wissenschaftliche Zoologie 90, 73136.Google Scholar
Goldschmidt, R. (1909). Das Nervensystem von Ascaris lumbricoides und Megalocephala. Ein Versuch, in den Aufbau eines einfachen Nervensystems einzudringen, Zweiter Teil. Zeitchrift für wissenschaftliche Zoologie 92, 306–57.Google Scholar
Grzywacz, M., Szkudlinsks, J. & Zandarowska, E. (1985). Pharmacological receptors of Ascaris lumbricoides suis L. Wiadomości Parazytologi 31, 153–61.Google ScholarPubMed
Harrow, I. D. & Gration, K. A. F. (1985). Mode of action of the anthelmintics morantel, pyrantel and levamisole on the muscle cell membrane of the nematode Ascaris suum. Pesticide Science 16, 662–72.CrossRefGoogle Scholar
Hesse, R. (1892). Über das Nervensystem von Ascaris lumbricoides und Ascaris megalocephala. Zeitschrift für wissenschaftliche Zoologie 90, 73136.Google Scholar
Hobson, A. D., Stephenson, W. & Beadle, L. C. (1952 a). Studies on the physiology of Ascaris lumbricoides. I. The relation of total osmotic pressure, conductivity and chloride content of the body fluid to that of the external environment. Journal of Experimental Biology 29, 121.Google Scholar
Hobson, A. D., Stephenson, W. & Eden, A. (1952 b). Studies on the physiology of Ascaris lumbricoides. II. The inorganic composition of the body fluid in relation to that of the environment. Journal of Experimental Biology 29, 22–9.CrossRefGoogle Scholar
Holden-Dye, L., Hewitt, G. M., Wann, K. T., Krogsgaard-Larsen, P. & Walker, R. J. (1988). Studies involving avermectin and the 4-aminobutyric acid (GABA) receptor of Ascaris suum muscle. Pesticide Science 24, 231–45.Google Scholar
Holden-Dye, L., Krogsgaard-Larsen, P., Neilsen, L. & Walker, R. J. (1989). GABA receptors on the somatic muscle cells of the parasitic nematode, Ascaris suum: stereoselectivity indicates similarity to a GABAa-type agonist recognition site. British Journal of Pharmacology 98, 841–50.CrossRefGoogle ScholarPubMed
Holden-Dye, L. & Walker, R. J. (1988). ZAPA, (Z)-3-[(amino iminomethyl)thio]-2-propenoic acid hydrochloride, a potent agonist at GABA receptors on the Ascaris muscle cell. British Journal of Pharmacology 95, 35.CrossRefGoogle Scholar
Horton, R. J. (1990). Benzimidazoles in a wormy world. Parasitology Today 6, 106.Google Scholar
Horvitz, R. H., Chalfie, M., Trent, C., Sulston, J. E. & Evans, P. D. (1982). Serotonin and octopamine in the nematode Caenorhabditis elegans. Science 206, 1012–14.CrossRefGoogle Scholar
Jarman, M. (1959). Electrical activity in the muscle cells of Ascaris lumbricoides. Nature, London 184, 1244.Google Scholar
Jarman, M. & Ellory, J. C. (1969). Effect of TTX on Ascaris somatic muscle. Experientia 25, 507.Google Scholar
Johnson, C. D. & Stretton, A. O. W. (1980). Neural control of locomotion in Ascaris: anatomy, electrophysiology and biochemistry. In Nematodes as Biological Models, vol. 1, pp. 159195. New York: Academic Press.Google Scholar
Johnson, C. D. & Stretton, A. O. W. (1985). Localization of choline acetyltransferase within identified motoneurons of the nematode Ascaris. Journal of Neuroscience 5, 1984–92.Google Scholar
Johnson, C. D. & Stretton, A. O. W. (1987). GABA-immunoreactivity in inhibitory motor neurons of the nematode Ascaris. Journal of Neuroscience 7, 223–35.CrossRefGoogle ScholarPubMed
Kass, I. S., Larsen, D. A., Wang, C. C. & Stretton, A. O. (1982). Ascaris suum: differential effects of avermectin B1a on the intact animal and neuromuscular strip preparations. Experimental Parasitology 54, 166–74.CrossRefGoogle ScholarPubMed
Kass, I. S., Stretton, A. O. & Wang, A. O. (1984). The effects of avermectin and drugs related to acetylcholine and 4-aminobutyric acid on neuromuscular transmission in Ascaris suum. Molecular and Biochemical Parasitology 13, 213–25.Google Scholar
Kass, I. S., Wang, C. C., Waldrond, J. P. & Stretton, A. O. W. (1980). Avermectin B1a, a paralysing anthelmintic that affects interneurones and inhibitory motorneurones in Ascaris. Proceedings of the National Academy of Sciences, USA 77, 6211–15.CrossRefGoogle ScholarPubMed
Lee, D. L. (1962). The distribution of esterase enzymes in Ascaris lumbricoides. Parasitology 52, 241–60.CrossRefGoogle Scholar
Lee, D. L. (1970). The fine structure of the excretory system in adult Nippostrongylus brasiliensis (Nematoda) and a suggested function for the excretory system of Anisakis larva (Nematoda: Anisakidae). Journal of Parasitology 59, 289–98.Google Scholar
Martin, R. E., Chauduri, J. & Donahue, M. J. (1988). Seronotin (5-Hydroxytryptamine) turnover in adult female Ascaris suum tissue. Comparative Biochemistry and Physiology 91C, 307–10.Google Scholar
Martin, R. E. & Donahue, M. J. (1987). Correlation of light chain phosphorylation and gamma aminobutyric acid receptors in Ascaris suum muscle. Comparative Biochemistry and Physiology 87, 23–9.Google ScholarPubMed
Martin, R. J. (1980). The effect of γ-aminobutyric acid on the input conductance and membrane potential of Ascaris muscle. British Journal of Pharmacology 71, 99106.CrossRefGoogle ScholarPubMed
Martin, R. J. (1982). Electrophysiological effects of piperazine and diethylcarbamazine on Ascaris suum somatic muscle. British Journal of Pharmacology 77, 255–65.Google Scholar
Martin, R. J. (1985 a) γ-aminobutyric acid- and piperazine-activated single channel currents from Ascaris suum body muscle. British Journal of Pharmacology 84, 445–61.Google Scholar
Martin, R. J. (1985 b) Chemotherapy of helminth infection: nematocides, fascioliacides. In Introduction to Veterinary Pharmacology (ed. Alexander, F. A.), pp. 355373, London: Longman.Google Scholar
Martin, R. J. (1987). The γ-aminobutyric acid receptor of Ascaris as a target for anthelmintics. Biochemical Society Transactions 17, 61–5.CrossRefGoogle Scholar
Martin, R. J., Kusel, J. R. & Pennington, A. J. (1990). Surface properties of membrane vesicles prepared from muscle cells of Ascaris suum. Journal of Parasitology 76, 340–8.Google Scholar
Martin, R. J. & Pennington, A. J. (1989). A patch-clamp study of effects of dihydroavermectin on Ascaris muscle. British Journal of Pharmacology 98, 747–56.CrossRefGoogle ScholarPubMed
Mellanby, H. (1955). The identification and estimation of acetylcholine in three parasitic nematodes (Ascaris lumbricoides, Litomosoides carinii, and the microfilariae of Dirofilaria repens). Parasitology 45, 287–94.Google Scholar
Natoff, I. L. (1969). The pharmacology of the cholinoceptor in muscle preparations of Ascaris lumbricoides var. suum. British Journal of Pharmacology 37, 251–7.CrossRefGoogle ScholarPubMed
Norton, S. & Beer, E. J.de (1957). Investigations on the action of piperazine on Ascaris lumbricoides. American Journal of Tropical Medicine 6, 898905.Google Scholar
Onuaguluchi, G. (1989). Some aspects of the pharmacology and physiology of the Ascaris suum muscle. Archives of International Pharmacodynamics and Therapeutics 298, 264–75.Google ScholarPubMed
Pennington, A. J. & Martin, R. J. (1990). A patch-clamp study of acetylcholine-activated ion channels in Ascaris suum muscle. Journal of Experimental Biology (In press).CrossRefGoogle ScholarPubMed
Rosenbluth, J. (1965 a). Ultrastructural organization of obliquely striated muscle fibres in Ascaris lumbricoides. Journal of Cell Biology 25, 495515.CrossRefGoogle ScholarPubMed
Rosenbluth, J. (1965 b). Ultrastructure of somatic muscle cells in Ascaris lumbricoides. II. Intermuscular junctions, neuromuscular junctions, and glycogen stores. Journal of Cell Biology 26, 579–91.CrossRefGoogle ScholarPubMed
Rosenbluth, J. (1967). Obliquely striated muscle. III. Contraction mechanism of Ascaris body muscle. Journal of Cell Biology 34, 1533.CrossRefGoogle Scholar
Rosenbluth, J. (1969). Ultrastructure of dyads in muscle fibres of Ascaris lumbricoides. Journal of Cell Biology 42, 817–25.Google Scholar
Rozhova, E. K., Malyutina, T. A. & Shishov, B. A. (1980). Pharmacological characteristics of cholinoreception in somatic muscle of the nematode Ascaris suum. General Pharmacology 11, 141–6.CrossRefGoogle Scholar
Saz, H. J. & Weil, A. (1962). A pathway of formation of α-methyl valerate by Ascaris lumbricoides. Journal of Biological Chemistry 237, 2053–6.CrossRefGoogle Scholar
Schneider, A. (1866). Monographie der Nematoden. Berlin.Google Scholar
Simmonds, M. A. & Turner, J. P. (1985). Antagonism of inhibitory amino acids by the steroid derivative RU5135. British Journal of Pharmacology 84, 631–6.CrossRefGoogle ScholarPubMed
Sithigorngul, P., Cowden, C., Guastella, J. & Stretton, A. O. W. (1989). Generation of monoclonal antibodies against a nematode peptide extract: another approach for identifying unknown neuropeptides. Journal of Comparative Neurology 284, 389–97.Google Scholar
Standen, O. D. (1955). Activity of piperazine, in vitro, against Ascaris lumbricoides. British Medical Journal 2, 20–2.Google Scholar
Stretton, A. O. W. (1976). Anatomy and development of the somatic musculature of the nematode of Ascaris, Journal of Experimental Biology 64, 773–88.Google Scholar
Stretton, A. O. W., Davis, R. E., Angstadt, J. D., Donmoyer, J. E. & Johnson, C. D. (1985). Neural control of behaviour in Ascaris. Trends in Neurosciences 8, 294300.CrossRefGoogle Scholar
Stretton, A. O. W., Fishpool, R. M., Southgate, E., Donmoyer, J. E., Walrond, J. P., Moses, J. E. R. & Kass, I. S. (1978). Structure and physiological activity of the motoneurons of the nematode Ascaris. Proceedings of the National Academy of Sciences, USA 75, 3493–7.Google Scholar
Sulston, J., Dew, M. & Brenner, S. (1975). Dopamine neurons in the nematode Caenorhabditis elegans. Journal of Comparative Neurology 163, 215–44.Google Scholar
Thorn, P. & Martin, R. J. (1987). A high-conductance calcium-dependent chloride channel in Ascaris suum muscle. Quarterly Journal of Experimental Physiology 72, 3149.Google Scholar
Rico, J.Toscano (1926). Sur la sensibilité de l' Ascaris à l'action de quelques drogues. Compte rendu des séances de la Société de Biologie, Paris 94, 921–3.Google Scholar
Tsang, V. C. & Saz, H. J. (1973). Demonstration and function of 2-methyl-butyrate racemase in Ascaris lumbricoides. Journal of Comparative Biochemistry and Physiology 45B, 617–23.Google Scholar
Walrond, J. P., Kass, I. S., Stretton, A. O. W. & Donmoyer, J. (1985). Identification of excitatory and inhibitory motoneurons in the nematode by electrophysiological techniques. Journal of Neuroscience 5, 18.CrossRefGoogle ScholarPubMed
Walrond, J. P. & Stretton, A. O. W. (1985). Reciprocal inhibition in the motor nervous system of the nematode Ascaris: direct control of ventral inhibitory motoneurons by dorsal excitatory motoneurons. Journal of Neuroscience 5, 915.Google Scholar
Wann, K. T. (1987). The electrophysiology of the somatic muscle cells of Ascaris suum and Ascaridia galli. Parasitology 94, 555–66.Google Scholar
Weisblat, D. A., Byerly, L. & Russel, R. L. (1976). Ionic mechanisms of electrical activity in the somatic muscle cell of the nematode Ascaris lumbricoides. Journal of Comparative Physiology 111, 93113.CrossRefGoogle Scholar
Weisblat, D. A. & Russel, R. L. (1976). Propagation of electrical activity in the nerve cord and muscle syncytium of the nematode Ascaris lumbricoides. Journal of Comparative Physiology 107, 293307.Google Scholar
Wermuth, C. G., Bourguignon, J. J., Schleiver, G., Gies, J. P., Schoenfelder, A., Melikian, A., Bouchet, M. T., Chantreaux, D., Molimard, J. C., Heaulme, M., Chambon, J. P. & Bizière, K. (1987). Synthesis and structure activity relationships of a series of arylaminopyridazine derivatives of GABA acting as selective GABAa antagonists. Journal of Medicinal Chemistry 30, 239–49.Google Scholar
White, J. G., Southgate, E., Thomson, J. N. & Brenner, S. (1976). The structure of the ventral cord of Caenorhabditis elegans. Philosophical Transactions of the Royal Society, Series B. 275, 298327.Google ScholarPubMed
White, J. G., Southgate, E., Thomson, J. N. & Brenner, S. (1986). The structure of the nervous system of Caenorhabditis elegans. Philosophical Transactions of the Royal Society, B. 314, 1340.Google Scholar
Willett, J. D. (1980). Control mechanisms in nematodes. In Nematodes as Biological Models, vol. 1 (ed. Zuckerman, B. M.), pp. 197225. New York: Academic Press.Google Scholar
Williams, T. L., Smith, D. A. S., Burton, N. R. & Stone, T. W. (1988). Amino acid pharmacology in neonatal slices: evidence for bimolecular actions from an extension of the Hill and Gaddum-Schild equations. British Journal of Pharmacology. 95, 805–10.CrossRefGoogle Scholar