Clustering of Voltage-Sensitive Sodium Channels on Axons Is Independent of Direct Schwann Cell Contact in the Dystrophic Mouse

Abstract

The distribution of voltage-sensitive sodium channels on axons in the dorsal and ventral spinal roots of the dystrophic mouse 129/ReJ–Lama^2dy was determined via immunocytochemistry. In these nerves there are regions in which Schwann cells fail to proliferate and myelinate axons in a normal manner, leaving bundles of closely packed large-diameter amyelinated axons. We have identified discrete and focal concentrations of sodium channel immunoreactivity on these axons by both confocal immunofluorescence and immunoelectron microscopy, using a peptide-derived polyclonal antibody. In addition, simultaneous labeling with an antibody recognizing neuronal-specific ankyrin_G revealed a distinct colocalization with the sodium channels on both normal and amyelinated axons. The presence of patches of sodium channels along with their anchoring protein on amyelinated axons in the absence of intervening Schwann cells demonstrates that axons can form and maintain independently these initial aggregations. This confirms that direct contact between Schwann cell and axon is not required for the formation of sodium channel patches of nodal dimensions and density. Furthermore, this strongly suggests that local transfer of sodium channels from Schwann cells to axons is not required for this process.