Sodium channel Na v 1.6 is localized at nodes of Ranvier, dendrites, and synapses
Open accessAbstract
Voltage-gated sodium channels perform critical roles for electrical signaling in the nervous system by generating action potentials in axons and in dendrites. At least 10 genes encode sodium channels in mammals, but specific physiological roles that distinguish each of these isoforms are not known. One possibility is that each isoform is expressed in a restricted set of cell types or is targeted to a specific domain of a neuron or muscle cell. Using affinity-purified isoform-specific antibodies, we find that Na v 1.6 is highly concentrated at nodes of Ranvier of both sensory and motor axons in the peripheral nervous system and at nodes in the central nervous system. The specificity of this antibody was also demonstrated with the Na v 1.6-deficient mouse mutant strain med , whose nodes were negative for Na v 1.6 immunostaining. Both the intensity of labeling and the failure of other isoform-specific antibodies to label nodes suggest that Na v 1.6 is the predominant channel type in this structure. In the central nervous system, Na v 1.6 is localized in unmyelinated axons in the retina and cerebellum and is strongly expressed in dendrites of cortical pyramidal cells and cerebellar Purkinje cells. Ultrastructural studies indicate that labeling in dendrites is both intracellular and on dendritic shaft membranes. Remarkably, Na v 1.6 labeling was observed at both presynaptic and postsynaptic membranes in the cortex and cerebellum. Thus, a single sodium channel isoform is targeted to different neuronal domains and can influence both axonal conduction and synaptic responses.
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Normally, Nav1.6 replaces fetal Nav1.2 at the nodes of Ranvier during the first few weeks of postnatal development.
“Normally, Nav1.6 replaces fetal Nav1.2 at the nodes of Ranvier during the first few weeks of postnatal development150.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [150]
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- Authors
- Caldwell, J. H., Schaller, K. L., Lasher, R. S., Peles, E., & Levinson, S. R.
- Affiliations
- University of Colorado Health (US)
- Salk Institute for Biological Studies (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-04-25
- Volume
- 97
- Issue
- 10
- Pages
- 5616-5620
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC25877
- OpenAlex
- W1997220636
- Cited by
- 649
- References
- 36
- Citations by year
- 2026: 16 · 2025: 21 · 2024: 16 · 2023: 16 · 2022: 18 · 2021: 29 · 2020: 31 · 2019: 28 · 2018: 22 · 2017: 27 · 2016: 21 · 2015: 30 · 2014: 30 · 2013: 26 · 2012: 21
- FWCI
- 8.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Minerva Foundation
- National Institutes of Health (5p01ns034375-05)
- National Institute of Neurological Disorders and Stroke (NS-34375, NS 26505, R01NS026505)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- Nav1.6 sodium channel, voltage-gated sodium channels, nodes of Ranvier, unmyelinated axons, Purkinje cells, cortical pyramidal neurons, isoform-specific antibodies, subcellular localization, axonal conduction, synaptic transmission
- MeSH terms
- Amino Acid Sequence, Animals, Axons, Brain, Brain Chemistry, Cell Membrane, Cerebellar Cortex, Cerebral Cortex, Dendrites, Molecular Sequence Data, Motor Neurons, Neurons, Afferent, Optic Nerve, Peptide Fragments, Purkinje Cells, Ranvier's Nodes, Retina, Sciatic Nerve, Synapses, Synaptic Vesicles, Sodium Channels, Pyramidal Cells, Mice, Rats
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