Clustering of neuronal sodium channels requires contact with myelinating Schwann cells

Efficient and rapid conduction of action potentials by saltatory conduction requires the clustering of voltage-gated sodium channels at nodes of Ranvi er. This clustering results from interactions between neurons and myelinati ng glia, although it has not been established whether this glial signal is contact-dependent or soluble. To investigate the nature of this signal, we examined sodium channel clustering in co-cultures of embryonic rat dorsal r oot ganglion neurons and Schwann cells. Cultures maintained under condition s promoting or preventing myelination were immunostained with antibodies ag ainst the alpha subunit of the sodium channel and against ankyrin(G), a cyt oskeletal protein associated with these channels. Consistent with previous in vivo studies (Vabnick et al., 1996), sodium channels and ankyrin G clust er at the onset of myelination. These clusters form adjacent to the ends of the myelinating Schwann cells and appear to fuse to form mature nodes. In contrast, sodium channels and ankyrin G do not cluster in neurons grown alo ne or in co-cultures where myelination is precluded by growing cells in def ined media. Conditioned media from myelinating co-cultures also failed to i nduce sodium channel or ankyrin G clusters in cultures of neurons alone. Fi nally, no clusters develop in the amyelinated portions of suspended fascicl es of dorsal root ganglia explants despite being in close proximity to myel inated segments in other areas of the dish. These results indicate that clu stering of sodium channels requires contact with myelinating Schwann cells.