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 myelinated central nervous system axons was studied during development of the optic nerve. In adult rats Kv1.1, Kv1.2, Kv1.6, and the cytoplasmic beta-subunit Kv beta 2 were colocalized in juxtaparanodal zones. During development, clustering of K+ channels lagged behind that for nodal Na+ channels by about 5 days. In contrast to the PNS, K+ channels were initially expressed fully segregated from nodes and paranodes, the latter identified by immunofluorescence of Caspr, a component of axoglial junctions. Clusters of K+ channels were first detected at postnatal day 14 (P14) at a limited number of sites. Expression increased until all juxtaparanodes had immunoreactivity by P40. Developmental studies in hypomyelinating Shiverer mice revealed dramatically disrupted axoglial junctions, aberrant Na+ channel clusters, and little or no detectable clustering of K+ channels at all ages. These results suggest that in the optic nerve, compact myelin and normal axoglial junctions are essential for proper K+ channel clustering and localization.