Abstract
Ion fluxes in mammalian myelinated axons are restricted to the nodes of Ranvier, where, in particular, voltage-gated Na+ channels are clustered at a high density. The node of Ranvier is separated from the internode by two distinct domains of the axolemma, the paranode and the juxtaparanode. Each axonal domain is characterized by the presence of a specific protein complex. Although oligodendrocytes and/or myelin membranes are believed to play some instructive roles in the organization of axonal domains, the mechanisms leading to their localized distribution are not well understood. In this paper we focused on the involvement of myelin sheaths in this domain organization and examined the distribution of axonal components in the optic nerves of wild type, hypomyelinating jimpy mice and demyelinating PLP transgenic mice. The results showed that the clustering of Na+ channels does not require junction-like structures to be formed between the glial processes and axons, but requires mature oligodendrocytes to be present in close vicinity.
Similar content being viewed by others
REFERENCES
Salzer, J. L. 1997. Clustering sodium channels at the node of Ranvier: Close encounters of the axo-glia kind. Neuron 18:843–846.
Pedraza, L., Huang, J. K., and Colman, D. R. 2001. Organizing principles of the axoglial apparatus. Neuron 30:335–344.
Hirano, A. and Dembitzer, H. M. 1982. Further studies on the transverse bands. J. Neurocytol. 11:851–856.
Wang, H., Kunkel, D. D., Martin, T. M., Schwartzkroin, P. A., and Tempel, B. L. 1993. Heteromultimeric K+ channels in terminal and juxtaparanodal regions of neurons. Nature 365:75–79.
Rasband, M. N., Trimmer, J. S., Schwarz, T. L., Levinson, S. R., Ellisman, M. H., Schachner, M., and Shrager, P. 1998. Potassium channel distribution, clustering, and function in remyelinating rat axons. J. Neurosci. 18:36–47.
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. J. Neurosci. 19:747–758.
Boiko, T., Rasband, M. N., Levinson, S. R., Galdwell, J. H., Mandel, G., Trimmer, J. S., and Matthews, G. 2001. Compact myelin dictates the differential targeting of two sodium channel isoforms in the same axon. Neuron 30:91–104.
Kaplan, M. R., Cho, M. H., Ullian, E. M., Isom, L. L., Levinson, S. R., and Barres, B. A. 2001. Differential control of clustering of the sodium channels Nav1.2 and Nav1.6 at developing CNS nodes of Ranvier. Neuron 30:105–119.
Peles, E., Nativ, M., Lustig, M., Grumet, M., Schilling, J., Martinez, R., Plowman, G. D., and Schlessinger, J. 1997. Identification of a novel contactin-associated transmembrane receptor with multiple domains implicated in protein-protein interactions. EMBO J. 16:978–988.
Einheber, S., Zanazzi, G., Ching, W., Scherer, S., Milner, T. A., Peles, E., and Salzer, J. L. 1997. The axonal membrane protein Caspr, a homologue of neurexin IV is a component of the septate-like paranodal junctions that assemble during myelination. J. Cell Biol. 139:1495–1506.
Kaplan, M. R., Meyer-Franke, A., Lambert, S., Bennett, V., Duncan, I. D., Levinson, S. R., and Barres, B. A. 1997. Induction of sodium channel clustering by oligodendrocytes. Nature 136:724–728.
Deerinck, T. J., Levinson, R. S., Bennett, V. G., and Ellisman. M. H., 1997. Clustering of voltage-sensitive sodium channels on axons is independent of direct Schwann cell contact in the dystrophic mouse. J. Neurosci. 17:5080–5088.
Lambert, S., Davis, J. Q., and Bennett, V. 1997. Morphogenesis of the node of Ranvier: Co-clusters of ankyrin and ankyrin-binding integral proteins define early developmental intermediates. J. Neurosci. 17:7025–7036.
Vabnick, I., Novakivuc, S. D., Levinson, S. R., Schachner, M., and Schrager, P. 1996. The clustering of axonal sodium channels during development of the peripheral nervous system. J. Neurosci. 16:4914–4922.
Dugandzija-Novakovic, S., Koszowski, A. G., Levinson, R. S., and Shrager, P. 1995. Clustering of Na+ channels and node of Ranvier formation in remyelianting axons. J. Neurosci. 15:492–503.
Rasband, M. N., Peles, E., Trimmer, J. S., Levinson, R., Lux, S. E., and Shrager, P. 1999. Dependence of nodal sodium channel clustering of paranodal axoglial contact in the developing CNS. J. Neurosci. 19:7516–7528.
Mathis, C., Denisenko-Nehrbass, N., Girault, J. A., and Borrelli, E. 2001. Essential role of oligodendrocytes in the formation and maintenance of central nervous system nodal regions. Development 128:4881–4890.
Arroyo, E. J., Xu, T., Grinspan, J., Lambert, S., Levinson, S. R., Brophy, P. J., Peles, E., and Scherer, S. S. 2002. Genetic dysmyelination alters the molecular architecture of the nodal region. J. Neurosci. 22:1726–1737.
Nave, K. A., Bloom, F. E., and Milner, R. J. 1987. A single nucleotide difference in the gene for myelin proteolipid protein defines the jimpy mutation in mouse. J. Nuerochem. 49:1873–1877.
Kagawa, T., Ikenaka, K., Inoue, Y., Kuriyama, S., Tsuji, T., Nakao, J., Nakajima, K., Aruga, J., Okano, H., and Mikoshiba, K. 1994. Glial cell degeneration and hypomyelination caused by overexpression of myelin proteolipid protein gene. Neuron 13:427–442.
Ishibashi, T., Dupree, J. L., Ikenaka, K., Hirahara, Y., Honke, K., Peles, E., Popko, B., Suzuki, K., Nishino, H., and Baba, H. 2002. A myelin galactolipid, sulfatide, is essential for maintenance of ion channels on myelinated axon but not essential for initial cluster formation. J. Neurosci. 22:6507–6514.
Trimmer, J. S. 1991. Immunological identification and characterization of a delayed rectifier K+ channels polypeptide in rat brain. Proc. Natl. Acad. Sci. U.S.A. 88:10764–10768.
Yamamura, T., Konola, J. T., Wekerle, H., and Lees, M. B. 1991. Monoclonal antibodies against myelin proteolipid protein: Identification and characterization of two major determinants. J. Neurochem. 57:1671–1680.
Baba, H., Akita, H., Ishibashi, T., Inoue, Y., Nakahira, K., and Ikenaka, K. 1999. Completion of myelin compaction, but not the attachment of oligodendroglial processes triggers K+ channel clustering. J. Neurosci. Res. 58:752–764.
Rasband, M. N. and Shrager, P. 2000. Ion channel sequestration in central nervous system axons. J. Physiol. 15:525 Pt 1:63–73.
Knapp, P. E. and Skoff, R. P. 1987. A defect in the cell cycle of neuroglia in the myelin deficient jimpy mouse. Dev. Brain Res. 35:301–306.
Duncan, I. D., Hammangm, J. P., Goda, S., and Quarles, R. H. 1989. Myelination in the jimpy mouse in the absence of proteolipid protein. Glia. 2:148–154.
Srinivasan, Y., Elmer, L., Davis, J., Bennett, V., and Angelides, K. 1988. Ankyrin and spectrin associate with voltage-dependent sodium channels in brain. Nature 333:177–180.
Kordeli, E., Lambert, S., and Bennett, V. 1995. Ankyrin G: A new ankyrin gene with neural-specific isoforms localized at the axonal initial segment and node of Ranvier. J. Biol. Chem. 270:2354–2359.
Jenkins, S. M. and Bennett, V. 2002. Developing nodes of Ranvier are defined by ankyrin-G clustering and are independent of paranodal axoglial adhesion. Proc. Natl. Acad. Sci. USA 99:2303–2308.
Inoue, Y., Kagawa, T., Matsumura, Y., Ikenaka, K., and Mikohsiba, K. 1996. Cell death of oligodendrocytes or demyelination induced by overexpression of proteolipid protein depending on expressed gene dosage. Neurosci. Res. 25:161–172.
Dupree, J. L., Girault, J. A., and Popko, B. 1999. Axo-glial interactions regulate the localization of axonal paranodal proteins. J. Cell Biol. 147:1145–1151.
Boyle, M. E. T., Berglund, E. O., Murai, K. K., Weber, L., Peles, E., and Ranscht, B. 2001. Contactin orchestrates assembly of septate-like junctions at the paranode in myelinated peripheral nerve. Neuron 30:385–397.
Skoff and Knapp, 1992. Biology and Chemistry. In Myelin. Martenson, R. E., (ed.). CRC Press, Boca Raton, FL, pp. 653–676.
Pribyl, T. M., Campagnoni, C. W., Kampf, K., Ellison, J. A., Landry, C. F., Kashima, T., McMahon, J., and Campagnoni, A. T. 1996. Expression of the myelin basic protein gene locus in neurons and oligodendrocytes in the human fetal central nervous system. J. Comp. Neurol. 374:342–353.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ishibashi, T., Ikenaka, K., Shimizu, T. et al. Initiation of Sodium Channel Clustering at the Node of Ranvier in the Mouse Optic Nerve. Neurochem Res 28, 117–125 (2003). https://doi.org/10.1023/A:1021608514646
Issue Date:
DOI: https://doi.org/10.1023/A:1021608514646