K+ channel distribution and clustering in developing and hypomyelinated axons of the optic nerve

The localization of Shaker-type K+ channels in specialized domains of myeli nated central nervous system axons was studied during development of the op tic nerve. In adult rats Kv1.1, Kv1.2, Kv1.6, and the cytoplasmic beta-subu nit Kv beta 2 were colocalized in juxtaparanodal zones. During development, clustering of K+ channels lagged behind that for nodal Na+ channels by abo ut 5 days. In contrast to the PNS, K+ channels were initially expressed ful ly segregated from nodes and paranodes, the latter identified by immunofluo rescence of Caspr, a component of axoglial junctions. Clusters of K+ channe ls were first detected at postnatal day 14 (P14) at a limited number of sit es. Expression increased until all juxtaparanodes had immunoreactivity by P 40. Developmental studies in hypomyelinating Shiverer mice revealed dramati cally disrupted axoglial junctions, aberrant Na+ channel clusters, and litt le or no detectable clustering of K+ channels at all ages. These results su ggest that in the optic nerve, compact myelin and normal axoglial junctions are essential for proper K+ channel clustering and localization.