Potassium Channel Distribution, Clustering, and Function in Remyelinating Rat Axons

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 precisely 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.