POTASSIUM CHANNEL DISTRIBUTION, CLUSTERING, AND FUNCTION IN REMYELINATING RAT AXONS

The K+ channel alpha-subunits Kv1.1 and Kv1.2 and the cytoplasmic beta -subunit KV beta 2 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, a nd during remyelination, the subcellular distributions of Kv1.1, Kv1.2 , and Kv beta 2 were reorganized. At 6 d postinjection (dpi), axons we re stripped of myelin, and K+ channels were found to be dispersed acro ss zones that extended into both nodal and internodal regions; a few d ays later they were undetectable. By 10 dpi, remyelination was underwa y, but Kv1.1 immunoreactivity was absent at newly forming nodes of Ran vier. By 14 dpi, K+ channels were detected but were in the nodal gap b etween Schwann cells. By 19 dpi, most new nodes had Kv1.1, Kv1.2, and Kv beta 2, which precisely colocalized. However, this nodal distributi on was transient. By 24 dpi, the majority of K+ channels was clustered within paranodal regions of remyelinated axons, leaving a gap that ov erlapped 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 ne ither 4-aminopyridine (4-AP) nor tetraethylammonium alters normal nerv e conduction. However, during remyelination, 4-AP profoundly increased both compound action potential amplitude and duration. The level of t his effect matched closely the nodal presence of these voltage-depende nt K+ channels. Our results suggest that K+ channels may have a signif icant effect on conduction during remyelination and that Schwann cells are important in K+ channel redistribution and clustering.