Summary
Rat sciatic nerve fibres were demyelinated by injection of lysolecithin and examined at several stages as Schwann cells proliferated, adhered, and initiated remyelination. Immunoperoxidase EM has been used to follow the clustering of Na+ channels that represents an early step in the formation of new nodes of Ranvier. At the peak of demyelination, 1 week postinjection, only isolated sites, suggestive of the original nodes, were labelled. As Schwann cells adhered and extended processes along the axons, regions of axonal Na+ channel immunoreactivity were often found just beyond their leading edges. These channel aggregates were associated only with the axolemma and Na+ channels were not detected on glial membranes. Sites with more than one cluster in close proximity and broadly labelled aggregates between Schwann cells suggested that new nodes of Ranvier formed as neighbouring Na+ channel groups merged. Schwann cells thus seem to play a major role in ion channel distributions in the axolemma. In all of these stages Na+ channel label was found primarily just outside the region of close contact between axon and Schwann cell. This suggests that Schwann cell adherence acts in part to exclude Na+ channels, or that diffusible substances are involved and can act some distance from regions of direct contact.
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References
Black, J. A., Foster, R. E. &Waxman, S. G. (1982) Rat optic nerve: freeze-fracture studies during development of myelinated axons.Brain Research 250, 1–20.
Bonnaud-Toulze, E. N. &Raine, C. S. (1980) Remodelling during remyelination in the peripheral nervous system.Neuropathology and Applied Neurobiology 6, 279–90.
Bostock, H. &Sears, T. A. (1978) The internodal axon membrane: electrical excitability and continuous conduction in segmental demyelination.Journal of Physiology 280, 273–301.
Chiu, S. Y. (1987) Sodium currents in axon-associated Schwann cells from adult rabbits.Journal of Physiology 386, 181–203.
Chiu, S. Y. (1993) Differential expression of sodium channels in acutely isolated myelinating and non-myelinating Schwann cells of rabbits.Journal of Physiology 470, 485–99.
Chiu, S. Y., Shrager, P. &Ritchie, J. M. (1984) neuronal-type Na+ and K+ channels in rabbit cultured Schwann cells.Nature 311, 156–7.
Devor, M., Keller, C. H., Deerinck, T. J., Levinson, S. R. &Ellisman, M. H. (1989) Na+ channel accumulation on axolemma of afferent endings in nerve end neuromas in Apteronotus.Neuroscience Letters 102, 149–54.
Dugandzija-Novakovic, R., Koszowski, A. G., Levinson, S. R. &Shrager, P. (1995) Clustering of Na channels and node of Ranvier formation in remyelinating axons.Journal of Neuroscience 15, 492–502.
Ellisman, M. H. (1979) Molecular specializations of the axon membrane at nodes of Ranvier are not dependent upon myelination.Journal of Neurocytology 8, 719–35.
Ellisman, M. H. &Levinson, S. R. (1982) Immunocytochemical localization of sodium channel distributions in the excitable membranes ofElectrophorus electricus.Proceedings of the National Academy of Sciences (USA) 79, 6707–11.
England, J. D., Gamboni, F., Levinson, S. R. &Finger, T. E. (1990) Changed distribution of sodium channels along demyelinated axons.Proceedings of the National Academy of Sciences (USA) 87, 6777–80.
England, J. D., Gamboni, F. &Levinson, S. R. (1991) Increased numbers of sodium channels form along demyelinated axons.Brain Reseach 548, 334–7.
Hall, S. M. &Gregson, N. A. (1971) Thein vivo and ultrastructural effects of injection of lysophosphatidyl choline into myelinated peripheral nerve fibres of the adult mouse.Journal of Cell Science 9, 769–89.
Hildebrand, C. (1989) Myelin sheath remodelling in remyelinated rat sciatic nerve.Journal of Neurocytology 18, 285–94.
Hines, M. &Shrager, P. (1991) A computational test of the requirements for conduction in demyelinated axons.Restorative Neurology and Neuroscience 3, 81–93.
Howe, J. R. &Ritchie, J. M. (1990) Sodium currents in Schwann cells from myelinated and non-myelinated nerves of neonatal and adult rabbits.Journal of Physiology 425, 169–210.
Joe, E. H. &Angelides, K. J. (1993) Clustering and mobility of voltage-dependent sodium channels during myelination.Journal of Neuroscience 13, 2993–3005.
Livingston, R. B., Pfenninger, K., Moor, H. &Akert, K. (1973) Specialized paranodal and interparanodal glialaxonal junctions in the peripheral and central nervous system: a freeze-etching study.Brain Research 58, 1–24.
Ritchie, J. M., Black, J. A., Waxman, S. G. &Angelides, K. J. (1990) Sodium channels in the cytoplasm of Schwann cells.Proceedings of the National Academy of Sciences (USA) 87, 9290–4.
Rosenbluth, J. (1979) Aberrant axon-Schwann cell junctions in dystrophic mouse nerves.Journal of Neurocytology 8, 655–72.
Rosenbluth, J. (1988) Role of glial cells in the differentiation and function of myelinated axons.International Journal of Developmental Neuroscience 6, 3–24.
Rubinstein, C. T. &Shrager, P. (1990) Remyelination of nerve fibers in the transected frog sciatic nerve.Brain Research 524, 303–12.
Schnapp, B., Peracchia, C. &Mugnaini, E. (1976) The paranodal axo-glial junction in the central nervous system studied with thin sections and freeze-fracture.Neuroscience 1, 181–90.
Shrager, P. (1988) Ionic channels and signal conduction in single remyelinating frog nerve fibres.Journal of Physiology 404, 695–712.
Shrager, P. (1989) Sodium channels in single demyelinated mammalian axons.Brain Research,483, 149–54.
Shrager, P. &Rubinstein, C. T. (1990) Optical measurement of conduction in single demyelinated axons.Journal of General Physiology 95, 867–89.
Shrager, P., Chiu, S. Y. &Ritchie, J. M. (1985) Voltagedependent sodium and potassium channels in mammamlian cultured Schwann cells.Proceedings of the National Academy of Sciences (USA) 82, 948–52.
Smith, K. J., Bostock, H. &Hall, S. M. (1982) Saltatory conduction precedes remyelination in axons demyelinated with lysophophatidyl choline.Journal of the Neurological Sciences 54, 13–31.
Tzoumaka, E., Novakovic, S. D., Levinson, S. R. &Shrager, P. (1995) Na+ channel aggregation in remyelinating mouse sciatic axons following transection.Glia 15, 188–94.
Wiley-Livingston, C. &Ellisman, M. H. (1980) Development of axonal membrane specializations defines nodes of Ranvier and precedes Schwann cell myelin elaboration.Developmental Biology 79, 334–55.
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Novakovic, S.D., Deerinck, T.J., Levinson, S.R. et al. Clusters of axonal Na+ channels adjacent to remyelinating Schwann cells. J Neurocytol 25, 403–412 (1996). https://doi.org/10.1007/BF02284811
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DOI: https://doi.org/10.1007/BF02284811