Dependence of Nodal Sodium Channel Clustering on Paranodal Axoglial Contact in the Developing CNS

• Published in: The Journal of neuroscience Vol. 19; no. 17; pp. 7516 - 7528
• Main Authors: Rasband, Matthew N, Peles, Elior, Trimmer, James S, Levinson, S. Rock, Lux, Samuel E, Shrager, Peter
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 01.09.1999; Society for Neuroscience
• Subjects: Action Potentials - physiology; Aging - physiology; Amino Acid Sequence; Animals; ankyrin 3/G; Axons - physiology; Caspr protein; Cell Adhesion Molecules, Neuronal; Cell Communication; channel clustering; Epitopes - chemistry; Gene Expression Regulation, Developmental; In Vitro Techniques; Mice; Mice, Inbred C3H; Mice, Neurologic Mutants; Molecular Sequence Data; Myelin Sheath - physiology; myelin-associated glycoprotein; Neural Conduction; Neuroglia - physiology; Oligodendroglia - physiology; Optic Nerve - growth & development; Optic Nerve - physiology; Ranvier's Nodes - physiology; Rats; Receptors, Cell Surface - analysis; Sodium Channels - analysis; Sodium Channels - genetics; Sodium Channels - physiology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.19-17-07516.1999

Na(+) channel clustering at nodes of Ranvier in the developing rat optic nerve was analyzed to determine mechanisms of localization, including the possible requirement for glial contact in vivo. Immunofluorescence labeling for myelin-associated glycoprotein and for the protein Caspr, a component of axoglial junctions, indicated that oligodendrocytes were present, and paranodal structures formed, as early as postnatal day 7 (P7). However, the first Na(+) channel clusters were not seen until P9. Most of these were broad, and all were excluded from paranodal regions of axoglial contact. The number of detected Na(+) channel clusters increased rapidly from P12 to P22. During this same period, conduction velocity increased sharply, and Na(+) channel clusters became much more focal. To test further whether oligodendrocyte contact directly influences Na(+) channel distributions, nodes of Ranvier in the hypomyelinating mouse Shiverer were examined. This mutant has oligodendrocyte-ensheathed axons but lacks compact myelin and normal axoglial junctions. During development Na(+) channel clusters in Shiverer mice were reduced in numbers and were in aberrant locations. The subcellular location of Caspr was disrupted, and nerve conduction properties remained immature. These results indicate that in vivo, Na(+) channel clustering at nodes depends not only on the presence of oligodendrocytes but also on specific axoglial contact at paranodal junctions. In rats, ankyrin-3/G, a cytoskeletal protein implicated in Na(+) channel clustering, was detected before Na(+) channel immunoreactivity but extended into paranodes in non-nodal distributions. In Shiverer, ankyrin-3/G labeling was abnormal, suggesting that its localization also depends on axoglial contact.