Potassium channel distribution, clustering, and function in remyelinating rat axons

Matthew N. Rasband, James Trimmer, Thomas L. Schwarz, S. Rock Levinson, Mark H. Ellisman, Melitta Schachner, Peter Shrager

Research output: Contribution to journalArticle

213 Scopus citations

Abstract

The K+ channel α-subunits Kv1.1 and Kv1.2 and the cytoplasmic β- subunit Kvβ2 were detected by immunofluorescence microscopy and found to be colocalized at juxtaparanodes in normal adult rat sciatic nerve. After demyelination by intraneural injection of lysolecithin, and during remyelination, the subcellular distributions of Kv1.1, Kv1.2, and Kvβ2 were reorganized. At 6 d postinjection (dpi), axons were stripped of myelin, and K+ channels were found to be dispersed across zones that extended into both nodal and internodal regions; a few days later they were undetectable. By 10 dpi, remyelination was underway, but Kv1.1 immunoreactivity was absent at newly forming nodes of Ranvier. By 14 dpi, K+ channels were detected but were in the nodal gap between Schwann cells. By 19 dpi, most new nodes had Kv1.1, Kv1.2, and Kvβ2, which precise y colocalized. However, this nodal distribution was transient. By 24 dpi, the majority of K+ channels was clustered within paranodal regions of remyelinated axons, leaving a gap that overlapped with Na+ channel immunoreactivity. Inhibition of Schwann cell proliferation delayed both remyelination and the development of the K+ channel distributions described. Conduction studies indicate that neither 4- aminopyridine (4-AP) nor tetraethylammonium alters normal nerve conduction. However, during remyelination, 4-AP profoundly increased both compound action potential amplitude and duration. The level of this effect matched closely the nodal presence of these voltage-dependent K+ channels. Our results suggest that K+ channels may have a significant effect on conduction during remyelination and that Schwann cells are important in K+ channel redistribution and clustering.

Original languageEnglish (US)
Pages (from-to)36-47
Number of pages12
JournalJournal of Neuroscience
Volume18
Issue number1
StatePublished - 1998
Externally publishedYes

Keywords

  • Axons
  • Demyelination
  • Node of Ranvier
  • Potassium channels
  • Remyelination
  • Schwann cells

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Rasband, M. N., Trimmer, J., Schwarz, T. L., Levinson, S. R., Ellisman, M. H., Schachner, M., & Shrager, P. (1998). Potassium channel distribution, clustering, and function in remyelinating rat axons. Journal of Neuroscience, 18(1), 36-47.