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Dependence of Nodal Sodium Channel Clustering on Paranodal Axoglial Contact in the Developing CNS
Open accessAbstract
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.
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“Deficits in myelination and oligodendrocyte maturation can also lead to impaired formation of the nodes of Ranvier (Kaplan et al., 2001; Rasband et al., 1999; Tanaka et al., 2009).”
From Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination (2016) · cites this paper as Rasband et al., 1999
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Self-citation
Metadata
- Authors
- Rasband, M. N., Peles, E., Trimmer, J. S., Levinson, S. R., Lux, S. E., & Shrager, P.
- Affiliations
- Weizmann Institute of Science (IL)
- Stony Brook University (US)
- University of Colorado Denver (US)
- Boston Children's Hospital (US)
- University of Rochester Medicine (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1999-09-01
- Volume
- 19
- Issue
- 17
- Pages
- 7516-7528
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6782503
- OpenAlex
- W1788586683
- Cited by
- 325
- References
- 58
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 4 · 2022: 3 · 2021: 7 · 2020: 18 · 2019: 9 · 2018: 7 · 2017: 5 · 2016: 17 · 2015: 9 · 2014: 11 · 2013: 14 · 2012: 8
- FWCI
- 5.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Multiple Sclerosis Society
- National Institutes of Health (5p01ns034375-05, NS34375)
- National Heart, Lung, and Blood Institute (P01HL032262)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK034083)
- National Institute of Neurological Disorders and Stroke (NS-34375, R01NS017965, NS34383, NS 17965, R01NS034383, R37NS034383)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- nodes of Ranvier, paranodal junctions, oligodendrocytes, optic nerve development, myelination, myelin-associated glycoprotein, Caspr, shiverer mice, hypomyelination, nerve conduction velocity
- MeSH terms
- Action Potentials, Aging, Amino Acid Sequence, Animals, Epitopes, Axons, Cell Communication, Mice, Inbred C3H, Mice, Neurologic Mutants, Molecular Sequence Data, Myelin Sheath, Neural Conduction, Neuroglia, Oligodendroglia, Optic Nerve, Ranvier's Nodes, Receptors, Cell Surface, Sodium Channels, Cell Adhesion Molecules, Neuronal, Gene Expression Regulation, Developmental, Mice, Rats, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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