Compact myelin dictates the differential targeting of two sodium channel isoforms in the same axon

Voltage-dependent sodium channels are uniformly distributed along unmyelina ted axons, but are highly concentrated at nodes of Ranvier in myelinated ax ons. Here, we show that this pattern is associated with differential locali zation of distinct sodium channel a subunits to the unmyelinated and myelin ated zones of the same retinal ganglion cell axons. In adult axons, Na(v)1. 2 is localized to the unmyelinated tone, whereas Na(v)1.6 is specifically t argeted to nodes. During development, Na(v)1.2 is expressed first and becom es clustered at immature nodes of Ranvier, but as myelination proceeds, Na( v)1.6 replaces Na(v)1.2 at nodes. In Shiverer mice, which lack compact myel in, Na(v)1.2 is found throughout adult axons, whereas little Na(v)1.6 is de tected. Together, these data show that sodium channel isoforms are differen tially targeted to distinct domains of the same axon in a process associate d with formation of compact myelin.