INDUCTION OF SODIUM-CHANNEL CLUSTERING BY OLIGODENDROCYTES

As oligodendrocytes wrap axons of the central nervous system (CNS) wit h insulating myelin sheaths, sodium channels that are initially contin uously distributed along axons become segregated into regularly spaced gaps in the myelin called nodes of Ranvier(1). It is not known whethe r the regular spacing of nodes results from regularly spaced glial con tacts or is instead intrinsically specified by the axonal cytoskeleton . Contact with Schwann cells induces clustering of sodium channels alo ng the axons of peripheral neurons in vitro and in vivo(2-4). Similarl y, it has been suggested that astrocyte contact induces clustering of sodium channels along CNS axons(5,6). Here we show that oligodendrocyt es are necessary for clustering of sodium channels in vitro and in viv o. The induction, but not the maintenance, of sodium-channel clusterin g along the axons of highly purified rat retinal ganglion cells in cul ture depends on a protein secreted by oligodendrocytes. Surprisingly, the oligodendrocyte-induced clusters are regularly spaced at the predi cted interval in the absence of glial-axonal contact. Mutant rats that are deficient in oligodendrocytes develop few axonal sodium channel c lusters in vivo. These results demonstrate a crucial role for oligoden drocytes in inducing clustering of sodium channels.