Clustering of voltage-dependent sodium channels on axons depends on Schwann cell contact.
In myelinated nerves, segregation of voltage-dependent sodium channels to nodes of Ranvier is crucial for saltatory conduction along axons. As sodium channels associate and colocalize with ankyrin at nodes of Ranvier, one possibility is that sodium channels are recruited and immobilized at axonal sites which are specified by the subaxolemmal cytoskeleton, independent of glial cell contact. Alternatively, segregation of channels at distinct sites along the axon may depend on glial cell contact. To resolve this question, we have examined the distribution of sodium channels, ankyrin and spectrin in myelination-competent cocultures of sensory neurons and Schwann cells by immunofluorescence, using sodium channel-, ankyrin- and spectrin-specific antibodies. In the absence of Schwann cells, sodium channels, ankyrin and spectrin are homogeneously distributed on sensory axons. When Schwann cells are introduced into these cultures, the distribution of sodium channels dramatically changes so that channel clusters on axons are abundant, but ankyrin and spectrin remain homogeneously distributed. Addition of latex beads or Schwann cell membranes does not induce channel clustering. Our results suggest that segregation of sodium channels on axons is highly dependent on interactions with active Schwann cells and that continuing axon-glial interactions are necessary to organize and maintain channel distribution during differentiation of myelinated axons.
Joe
E H
EH
Department of Molecular Physiology, Baylor College of Medicine, Houston, Texas 77030.
Angelides
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K
D000818:Animals; D017487:Ankyrins; D001369:Axons / Q000648:ultrastructure; D001798:Blood Proteins / Q000378:metabolism; D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000648:ultrastructure*; D051381:Rats; D011919:Rats, Inbred Strains; D012583:Schwann Cells / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology*; D013049:Spectrin / Q000378:metabolism
D017487:Ankyrins; D001798:Blood Proteins; D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; D015222:Sodium Channels; D013049:Spectrin