Distribution of sodium channels in chronically demyelinated spinal cord axons: immuno-ultrastructural localization and electrophysiological observations

The immuno-ultrastructural localization of voltage-sensitive sodium channels was demonstrated within a central demyelinating lesion induced in the rat spinal cord by ethidium bromide/irradiation using polyclonal antibody 7493. Antibody 7493 has previously been shown to immunostain intensely axon mem...

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Veröffentlicht in:Brain research 1991-03, Vol.544 (1), p.59-70
Hauptverfasser: Black, J.A., Felts, P., Smith, K.J., Kocsis, J.D., Waxman, S.G.
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Smith, K.J.
Kocsis, J.D.
Waxman, S.G.
description The immuno-ultrastructural localization of voltage-sensitive sodium channels was demonstrated within a central demyelinating lesion induced in the rat spinal cord by ethidium bromide/irradiation using polyclonal antibody 7493. Antibody 7493 has previously been shown to immunostain intensely axon membrane at nodes of Ranvier, and also perinodal astrocyte processes. At 25–35 days post injection/irradiation, the central portion of the demyelinating lesion is populated with chronically demyelinated axons and there is an absence of glial processes. Sodum channel immunoreactivity was not observed on the chronically demyelinated axolemma within this central portion of the lesion. Within the peripheral portion of the lesion demyelinated axons were occasionally abutted by astrocyte and Schwann cell processes. At these focal sites of apposition, the axon membrane displayed intense sodium channel immunoreactivity, while the abutting astrocyte and Schwann cell processes did not exhibit immunostaining. Also in the periphery of the lesion, some axons become ensheathed and myelinated by oligodendrocytes and Schwann cells. The axon membrane of circumferentially ensheathed axons displayed antibody 7493 immunostaining, and this immunoreactivity persisted on the axolemma until the ensheathing cytoplasmic processes compacted into myelin. Internodal axon membrane beneath the myelin sheath did not display sodium channel immunoreactivity, though (putative) developing nodal axon membrane adjacent to terminal paranodal loops exhibited robust sodium channel staining. Electrophysiological recordings within the ethidium bromide/irradiation lesion demonstrated that at least some axons conducted action potentials within the lesion, while others exhibited conduction block. These results indicate that there is a reorganization of sodium channels within the axon membrane of chronically demyelinated central axons.
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Psychology</topic><topic>Immunocytochemistry</topic><topic>Impulse conduction</topic><topic>Membrane structure</topic><topic>Microscopy, Immunoelectron</topic><topic>Myelin Sheath - physiology</topic><topic>Neuroglia - physiology</topic><topic>Rats</topic><topic>Sodium channel</topic><topic>Sodium Channels - drug effects</topic><topic>Sodium Channels - physiology</topic><topic>Sodium Channels - ultrastructure</topic><topic>Spinal cord</topic><topic>Spinal Cord - physiology</topic><topic>Spinal Cord - ultrastructure</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Black, J.A.</creatorcontrib><creatorcontrib>Felts, P.</creatorcontrib><creatorcontrib>Smith, K.J.</creatorcontrib><creatorcontrib>Kocsis, J.D.</creatorcontrib><creatorcontrib>Waxman, S.G.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Black, J.A.</au><au>Felts, P.</au><au>Smith, K.J.</au><au>Kocsis, J.D.</au><au>Waxman, S.G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Distribution of sodium channels in chronically demyelinated spinal cord axons: immuno-ultrastructural localization and electrophysiological observations</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>1991-03-22</date><risdate>1991</risdate><volume>544</volume><issue>1</issue><spage>59</spage><epage>70</epage><pages>59-70</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><coden>BRREAP</coden><abstract>The immuno-ultrastructural localization of voltage-sensitive sodium channels was demonstrated within a central demyelinating lesion induced in the rat spinal cord by ethidium bromide/irradiation using polyclonal antibody 7493. Antibody 7493 has previously been shown to immunostain intensely axon membrane at nodes of Ranvier, and also perinodal astrocyte processes. At 25–35 days post injection/irradiation, the central portion of the demyelinating lesion is populated with chronically demyelinated axons and there is an absence of glial processes. Sodum channel immunoreactivity was not observed on the chronically demyelinated axolemma within this central portion of the lesion. Within the peripheral portion of the lesion demyelinated axons were occasionally abutted by astrocyte and Schwann cell processes. At these focal sites of apposition, the axon membrane displayed intense sodium channel immunoreactivity, while the abutting astrocyte and Schwann cell processes did not exhibit immunostaining. Also in the periphery of the lesion, some axons become ensheathed and myelinated by oligodendrocytes and Schwann cells. The axon membrane of circumferentially ensheathed axons displayed antibody 7493 immunostaining, and this immunoreactivity persisted on the axolemma until the ensheathing cytoplasmic processes compacted into myelin. Internodal axon membrane beneath the myelin sheath did not display sodium channel immunoreactivity, though (putative) developing nodal axon membrane adjacent to terminal paranodal loops exhibited robust sodium channel staining. Electrophysiological recordings within the ethidium bromide/irradiation lesion demonstrated that at least some axons conducted action potentials within the lesion, while others exhibited conduction block. These results indicate that there is a reorganization of sodium channels within the axon membrane of chronically demyelinated central axons.</abstract><cop>London</cop><cop>Amsterdam</cop><cop>New York, NY</cop><pub>Elsevier B.V</pub><pmid>1649663</pmid><doi>10.1016/0006-8993(91)90885-Y</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; Elsevier ScienceDirect Journals
subjects 4-Aminopyridine - pharmacology
Action potential
Action Potentials - drug effects
Anatomy
Animals
Antibodies
Axons - drug effects
Axons - physiology
Axons - ultrastructure
Biological and medical sciences
Central nervous system
Demyelination
Electric Stimulation
Electrophysiology - methods
Fundamental and applied biological sciences. Psychology
Immunocytochemistry
Impulse conduction
Membrane structure
Microscopy, Immunoelectron
Myelin Sheath - physiology
Neuroglia - physiology
Rats
Sodium channel
Sodium Channels - drug effects
Sodium Channels - physiology
Sodium Channels - ultrastructure
Spinal cord
Spinal Cord - physiology
Spinal Cord - ultrastructure
Vertebrates: nervous system and sense organs
title Distribution of sodium channels in chronically demyelinated spinal cord axons: immuno-ultrastructural localization and electrophysiological observations
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