Abnormal sodium channel distribution in optic nerve axons in a model of inflammatory demyelination
Myelinated fibres are characterized by the aggregation of Nav1.6 sodium channels within the axon membrane at nodes of Ranvier, where their presence supports saltatory conduction. In this study, we used immunocytochemical methods to study the organization of sodium channels along axons in experimenta...
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Published in | Brain (London, England : 1878) Vol. 126; no. 7; pp. 1552 - 1561 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Oxford University Press
01.07.2003
Oxford Publishing Limited (England) |
Subjects | |
Online Access | Get full text |
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Summary: | Myelinated fibres are characterized by the aggregation of Nav1.6 sodium channels within the axon membrane at nodes of Ranvier, where their presence supports saltatory conduction. In this study, we used immunocytochemical methods to study the organization of sodium channels along axons in experimental allergic encephalomyelitis (EAE), a model of multiple sclerosis. We studied axons within the optic nerve, a CNS tract commonly affected in multiple sclerosis, and their cell bodies of origin (retinal ganglion cells), using subtype‐specific antibodies generated against sodium channel subtypes Nav1.1, Nav1.2, Nav1.3 and Nav1.6, which previously have been shown to be expressed by retinal ganglion cells. We demonstrate a significant switch from Nav1.6 to Nav1.2 expression in the optic nerve in EAE; there was a reduction in frequency of Nav1.6‐positive nodes (84.5% Nav1.6‐immunopositive nodes in control versus 32.9% in EAE) and increased frequency of Nav1.2‐positive nodes (11.8% Nav1.2 immunopositive nodes in control versus 74.9% in EAE). Moreover, we observed a significant increase in the number of linear (presumably demyelinated) axonal profiles demonstrating extended diffuse immunostaining for Nav1.2 in EAE versus control optic nerves. These changes within the optic nerve are paralleled by decreased levels of Nav1.6 and increased Nav1.2 protein, together with increased levels of Nav1.2 mRNA, within retinal ganglion cells in EAE. Our findings of a loss of Nav1.6 and increased expression of Nav1.2 suggest that electrogenesis in EAE may revert to a stage similar to that observed in immature retinal ganglion cells in which Nav1.2 channels support conduction of action potentials along axons. |
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Bibliography: | istex:A89006A2676E7CFB4D733B83187D40634C464E08 ark:/67375/HXZ-VXH7R5NR-0 local:awg153 Correspondence to: Stephen G. Waxman, MD, PhD, Department of Neurology LCI 707, Yale University School of Medicine, 333 Cedar Street, PO Box 208018, New Haven, CT 06520‐8018, USA E‐mail: stephen.waxman@yale.edu ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0006-8950 1460-2156 1460-2156 |
DOI: | 10.1093/brain/awg153 |