Differential control of clustering of the sodium channels Na(v)1.2 and Na(v)1.6 at developing CNS nodes of ranvier

Na(v)1.6 is the main sodium channel isoform at adult nodes of Ranvier. Here , we show that Na(v)1.2 and its beta2 subunit, but not Na(v)1.6 or beta1, a re clustered in developing central nervous system nodes and that clustering of Na(v)1.2 and Na(v)1.6 is differentially controlled. Oligodendrocyte-con ditioned medium is sufficient to induce clustering of Na(v)1.2 alpha and be ta2 subunits along central nervous system axons in vitro. This clustering i s regulated by electrical activity and requires an intact actin cytoskeleto n and synthesis of a non-sodium channel protein. Neither soluble- or contac t-mediated glial signals induce clustering of Na(v)1.6 or beta1 in a nonmye linating culture system. These data reveal that the sequential clustering o f Na(v)1.2 and Na(v)1.6 channels is differentially controlled and suggest t hat myelination induces Na(v)1.6 clustering.