Sodium channel Na(v)1.6 is expressed along nonmyelinated axons and it contributes to conduction.
Nodes of Ranvier in myelinated fibers exhibit a complex architecture in which specific molecules organize in distinct nodal, paranodal and juxtaparanodal domains to support saltatory conduction. The clustering of sodium channel Na(v)1.6 within the nodal membrane has led to its identification as the major nodal sodium channel in myelinated axons. In contrast, much less is known about the molecular architecture of nonmyelinated fibers. In the present study, Na(v)1.6 is shown to be a significant component of nonmyelinated PNS axons. In DRG C-fibers, Na(v)1.6 is distributed continuously from terminal receptor fields in the skin to the dorsal root entry zone in the spinal cord. Na(v)1.6 is also present in the nerve endings of corneal C-fibers. Analysis of compound action potential recordings from wildtype and med mice, which lack Na(v)1.6, indicates that Na(v)1.6 plays a functional role in nonmyelinated fibers where it contributes to action potential conduction. These observations indicate that Na(v)1.6 functions not only in saltatory conduction in myelinated axons but also in continuous conduction in nonmyelinated axons.