Hostname: page-component-848d4c4894-mwx4w Total loading time: 0 Render date: 2024-06-19T11:21:57.547Z Has data issue: false hasContentIssue false
  • English
  • Français

A model of tight junction function in central nervous system myelinated axons

Published online by Cambridge University Press:  27 January 2010

Alexander Gow  and
Jerome Devaux
Alexander Gow*
Affiliation:
Center for Molecular Medicine and Genetics Carman and Ann Adams Department of Pediatrics Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA
Jerome Devaux
Affiliation:
Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, PA, USA Département Signalisation Neuronale CRN2M, UMR 6231, CNRS, Université de la Méditerranée-Université Paul Cézanne, IFR Jean Roche Marseille, France
*
Correspondence should be addressed to: Alexander Gow Center for Molecular Medicine and Genetics, 3216 Scott Hall 540 E Canfield Avenue, Wayne State University School of MedicineDetroit, MI 48201, USA phone: (313) 577-9401 Fax: (313) 577-1632 email: agow@med.wayne.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

The insulative properties of myelin sheaths in the central and peripheral nervous systems (CNS and PNS) are widely thought to derive from the high resistance and low capacitance of the constituent membranes. Although this view adequately accounts for myelin function in large diameter fibers, it poorly reflects the behavior of small fibers that are prominent in many regions of the CNS. Herein, we develop a computational model to more accurately represent conduction in small fibers. By incorporating structural features that, hitherto, have not been simulated, we demonstrate that myelin tight junctions (TJs) improve saltatory conduction by reducing current flow through the myelin, limiting axonal membrane depolarization and restraining the activation of ion channels beneath the myelin sheath. Accordingly, our simulations provide a novel view of myelin by which TJs minimize charging of the membrane capacitance and lower the membrane time constant to improve the speed and accuracy of transmission in small diameter fibers. This study establishes possible mechanisms whereby TJs affect conduction in the absence of overt perturbations to myelin architecture and may in part explain the tremor and gait abnormalities observed in Claudin 11-null mice.

Keywords

Axoglial junctionsmodelingparanodalschizophreniamultiple sclerosis
Type
Research Article
Information
Neuron Glia Biology , Volume 4 , Issue 4 , November 2008 , pp. 307 - 317
Copyright
Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aboitiz, F., Scheibel, A.B., Fisher, R.S. and Zaidel, E. (1992) Fiber composition of the human corpus callosum. Brain Research 598, 143–153.CrossRefGoogle ScholarPubMed
Agrawal, D., Hawk, R., Avila, R.L., Inouye, H. and Kirschner, D.A. (2009) Internodal myelination during development quantitated using X-ray diffraction. Journal of Structural Biology. doi: 10.1016/j.jsb.2009.06.019CrossRefGoogle ScholarPubMed
Barrett, E.F. and Barrett, J.N. (1982) Intracellular recording from vertebrate myelinated axons: mechanism of the depolarizing afterpotential. Journal of Physiology 323, 117–144.CrossRefGoogle ScholarPubMed
Berthold, C.-H. and Rydmark, M. (1995) Morphology of normal peripheral axons. In Waxman, S.G., Kocsis, J.D. and Stys, P.K. (eds) The Axon. Oxford University Press, pp. 13–48.CrossRefGoogle Scholar
Bhat, M.A., Rios, J.C., Lu, Y., Garcia-Fresco, G.P., Ching, W., Martin, M.S. et al. (2001) Axon–glia interactions and the domain organization of myelinated axons requires neurexin iv/caspr/paranodin. Neuron 30, 369–383.CrossRefGoogle ScholarPubMed
Blight, A.R. (1983) Axonal physiology of chronic spinal cord injury in the cat: intracellular recording in vitro. Neuroscience 10, 1471–1486.CrossRefGoogle ScholarPubMed
Blight, A.R. (1985) Computer simulation of action potentials and afterpotentials in mammalian myelinated axons: the case for a lower resistance myelin sheath. Neuroscience 15, 13–31.CrossRefGoogle ScholarPubMed
Blight, A.R. and Someya, S. (1985) Depolarizing afterpotentials in myelinated axons of mammalian spinal cord. Neuroscience 15, 1–12.CrossRefGoogle ScholarPubMed
Boyd, I.A. and Kalu, K.U. (1979) Scaling factor relating conduction velocity and diameter for myelinated afferent nerve fibres in the cat hind limb. Journal of Physiology 289, 277–297.CrossRefGoogle ScholarPubMed
Boyle, M.E., Berglund, E.O., Murai, K.K., Weber, L., Peles, E. and Ranscht, B. (2001) Contactin orchestrates assembly of the septate-like junctions at the paranode in myelinated peripheral nerve. Neuron 30, 385–397.CrossRefGoogle ScholarPubMed
Brill, M.H., Waxman, S.G., Moore, J.W. and Joyner, R.W. (1977) Conduction velocity and spike configuration in myelinated fibres: computed dependence on internode distance. Journal of Neurology Neurosurgery and Psychiatry 40, 769–774.CrossRefGoogle ScholarPubMed
Cajal, S.R. (1899) Texture of the Nervous System of Man and the Vertebrates. Berlin: Springer.Google Scholar
Chiu, S.Y. and Schwarz, W. (1987) Sodium and potassium currents in acutely demyelinated internodes of rabbit sciatic nerves. Journal of Physiology 391, 631–649.CrossRefGoogle ScholarPubMed
Claude, P. and Goodenough, D.A. (1973) Fracture faces of zonulae occludentes from “tight” and “leaky” epithelia. Journal of Cell Biology 58, 390–400.CrossRefGoogle ScholarPubMed
Clausen, C. (1989) Impedance analysis in tight epithelia. Methods in Enzymology 171, 628–642.CrossRefGoogle ScholarPubMed
del Rio-Hortega, P. (1928) Tercera aportacion al conocimiento morfologico e interpretacion funcional de la oligodendroglia. Memorias Real de la Sociedad Espanola de Historia Natural 14, 5–119.Google Scholar
Devaux, J.J. and Gow, A. (2008) Tight junctions potentiate the insulative properties of small CNS myelinated axons. Journal of Cell Biology 183, 909–921.CrossRefGoogle ScholarPubMed
Dupree, J.L., Coetzee, T., Blight, A., Suzuki, K. and Popko, B. (1998) Myelin galactolipids are essential for proper node of Ranvier formation in the CNS. Journal of Neuroscience 18, 1642–1649.CrossRefGoogle ScholarPubMed
Frankenhaeuser, B. and Huxley, A.F. (1964) The action potential in the myelinated nerve fiber of xenopus laevis as computed on the basis of voltage clamp data. Journal of Physiology 171, 302–315.CrossRefGoogle ScholarPubMed
Gow, A., Southwood, C.M., Li, J.S., Pariali, M., Riordan, G.P., Brodie, S.E. et al. (1999) CNS myelin and sertoli cell tight junction strands are absent In Osp/Claudin 11-Null Mice. Cell 99, 649–659.CrossRefGoogle ScholarPubMed
Halter, J.A. and Clark, J.W. Jr. (1991) A distributed-parameter model of the myelinated nerve fiber. Journal of Theoretical Biology 148, 345–382.CrossRefGoogle ScholarPubMed
Haroutunian, V., Katsel, P., Dracheva, S., Stewart, D.G. and Davis, K.L. (2007) Variations in oligodendrocyte-related gene expression across multiple cortical regions: implications for the pathophysiology of schizophrenia. International Journal of Neuropsychopharmacology 10, 565–573.CrossRefGoogle ScholarPubMed
Hartline, D.K. and Colman, D.R. (2007) Rapid conduction and the evolution of giant axons and myelinated fibers. Current Biology 17, R29–R35.CrossRefGoogle ScholarPubMed
Hines, M.L. and Carnevale, N.T. (1997) The NEURON simulation environment. Neural Computation 9, 1179–1209.CrossRefGoogle ScholarPubMed
Hines, M.L. and Carnevale, N.T. (2001) NEURON: a tool for neuroscientists. Neuroscientist 7, 123–135.CrossRefGoogle ScholarPubMed
Ibrahim, M., Butt, A.M. and Berry, M. (1995) Relationship between myelin sheath diameter and internodal length in axons of the anterior medullary velum of the adult rat. Journal of Neurological Science 133, 119–127.CrossRefGoogle ScholarPubMed
Ilyin, V.I., Katina, I.E., Lonskii, A.V., Makovsky, V.S. and Polishchuk, E.V. (1980) The Cole–Moore effect in nodal membrane of the frog Rana ridibunda: evidence for fast and slow potassium channels. Journal of Membrane Biology 57, 179–193.CrossRefGoogle ScholarPubMed
Janecki, A., Jakubowiak, A. and Steinberger, A. (1991) Regulation of transepithelial electrical resistance in two-compartment Sertoli cell cultures: in vitro model of the blood-testis barrier. Endocrinology 129, 1489–1496.CrossRefGoogle ScholarPubMed
Kampa, B.M., Letzkus, J.J. and Stuart, G.J. (2007) Dendritic mechanisms controlling spike-timing-dependent synaptic plasticity. Trends in Neurosciences 30, 456–463.CrossRefGoogle ScholarPubMed
Kirschner, D.A., Ganser, A.L. and Caspar, D.L.D. (1984) Diffraction studies of molecular organization and membrane interactions in myelin. In Morell, P. (ed.) Myelin. New York: Plenum, pp. 51–95.CrossRefGoogle Scholar
McIntyre, C.C., Richardson, A.G. and Grill, W.M. (2002) Modeling the excitability of mammalian nerve fibers: influence of afterpotentials on the recovery cycle. Journal of Neurophysiology 87, 995–1006.CrossRefGoogle ScholarPubMed
Morita, K., Sasaki, H., Fujimoto, K., Furuse, M. and Tsukita, S. (1999) Claudin-11/OSP-based tight junctions of myelin sheaths in brain and Sertoli cells in testis. Journal of Cell Biol. 145, 579–588.CrossRefGoogle ScholarPubMed
Peters, A. (1961) A radial component of central myelin sheaths. Journal of Biophysical and Biochemical Cytology 11, 733–735.CrossRefGoogle ScholarPubMed
Peters, A. (1966) The node of Ranvier in the central nervous system. Quarterly Journal of Experimental Physiology and Cognate Medical Sciences 51, 229–236.CrossRefGoogle ScholarPubMed
Rasminsky, M. and Sears, T.A. (1972) Internodal conduction in undissected demyelinated nerve fibres. Journal of Physiology 227, 323–350.CrossRefGoogle ScholarPubMed
Reuss, L. (2001) Tight junction permeability to ions and water. In Anderson, J.M. and Cereijido, M. (eds) Tight Junctions. New York: CRC Press, pp. 61–88.Google Scholar
Rosenbluth, J. (1995) Glial membranes and axoglial junctions. In Kettenmann, H. and Ransom, B.R. (eds) Neuroglia. Oxford: Oxford University Press, pp. 613–633.Google Scholar
Rosenbluth, J. (1999) A brief history of myelinated nerve fibers: one hundred and fifty years of controversy. Journal of Neurocytology 28, 251–262.CrossRefGoogle ScholarPubMed
Scherer, S.S. and Arroyo, E.J. (2002) Recent progress on the molecular organization of myelinated axons. Journal of Peripheral Nervous System 7, 1–12.CrossRefGoogle ScholarPubMed
Schnapp, B. and Mugnaini, E. (1978) Membrane architecture of myelinated fibers as seen by freeze-fracture. In Waxman, S.G. (ed.) Physiology and Pathobiology of Axons. New York: Raven, pp. 83–123.Google Scholar
Schwarz, J.R. and Eikhof, G. (1987) Na currents and action potentials in rat myelinated nerve fibres at 20 and 37 degrees C. Pflugers Archiv 409, 569–577.CrossRefGoogle ScholarPubMed
Sherman, D.L., Tait, S., Melrose, S., Johnson, R., Zonta, B., Court, F.A. et al. (2005) Neurofascins are required to establish axonal domains for saltatory conduction. Neuron 48, 737–742.CrossRefGoogle ScholarPubMed
Shrager, P. (1993) Axonal coding of action potentials in demyelinated nerve fibers. Brain Research 619, 278–290.CrossRefGoogle ScholarPubMed
Southwood, C., He, C., Garbern, J., Kamholz, J., Arroyo, E. and Gow, A. (2004) CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure. Journal of Neuroscience 24, 11215–11225.CrossRefGoogle ScholarPubMed
Stephanova, D.I. and Bostock, H. (1996) A distributed-parameter model of the myelinated human motor nerve fibre: temporal and spatial distributions of electrotonic potentials and ionic currents. Biological Cybernetics 74, 543–547.CrossRefGoogle ScholarPubMed
Stewart, D.G. and Davis, K.L. (2004) Possible contributions of myelin and oligodendrocyte dysfunction to schizophrenia. International Review of Neurobiology 59, 381–424.CrossRefGoogle ScholarPubMed
Tasaki, I. (1955) New measurements of the capacity and the resistance of the myelin sheath and the nodal membrane of the isolated frog nerve fiber. Americal Journal of Physiology 181, 639–650.CrossRefGoogle ScholarPubMed
Tsukita, S., Furuse, M. and Itoh, M. (2001) Multifunctional strands in tight junctions. Nature Reviews Molecular Cell Biology 2, 285–293.CrossRefGoogle ScholarPubMed
Vabnick, I., Trimmer, J.S., Schwarz, T.L., Levinson, S.R., Risal, D. and Shrager, P. (1999) Dynamic potassium channel distributions during axonal development prevent aberrant firing patterns. Journal of Neuroscience 19, 747–758.CrossRefGoogle ScholarPubMed
Waxman, S.D. and Bangalore, L. (2004) Electrophysiological consequences of myelination. In Lazzarini, R.A. (ed.) Myelin Biology and Disorders. Amsterdam: Elsevier, pp. 117–141.Google Scholar
Waxman, S.G. and Bennett, M.V. (1972) Relative conduction velocities of small myelinated and non-myelinated fibres in the central nervous system. Nature New Biology 238, 217–219.CrossRefGoogle ScholarPubMed
Supplementary material: File

Gow and Devaux supplementary material

Legends for figs and tables

Download Gow and Devaux supplementary material(File)
File 158.2 KB
Supplementary material: Image

Gow and Devaux supplementary material

Fig. 1

Download Gow and Devaux supplementary material(Image)
Image 752.9 KB
Supplementary material: Image

Gow and Devaux supplementary material

Fig. 2

Download Gow and Devaux supplementary material(Image)
Image 4.9 MB
Supplementary material: Image

Gow and devaux supplementary material

Fig. 3

Download Gow and devaux supplementary material(Image)
Image 687.8 KB
Supplementary material: Image

Gow and Devaux supplementary material

Fig. 4

Download Gow and Devaux supplementary material(Image)
Image 510.3 KB
Supplementary material: Image

Gow and Devaux supplementary material

Fig. 5

Download Gow and Devaux supplementary material(Image)
Image 871.9 KB