抄録
Persistent sodium current plays important roles in neuronal excitabilities. Nav1.6, a widely expressed sodium channel isoform in CNS and PNS, is known as one of the major contributors of persistent currents in cell soma. On the other hand, Nav1.6 is localized at the axon initial segment (AIS) and node of Ranvier and thereby responsible for fast saltatory conduction of action potential along myelinated fibers, where, by classical measurements, persistent component is not so prominent. One possibility is that some factors in node and AIS may inhibit persistent current which could be a default property of Nav1.6 channel. We show that ankyrin G, which is required for clustering of Nav1.6 channels in node and AIS, significantly reduces persistent current of Nav1.6 channel in tsA201 cells and Xenopus oocyte. This inhibition was not observed in coexpresssion with another ankyrin isoform, ankyrin B. By testing chimeras between ankyrin G and B, it was shown that the membrane-binding domain in ankyrin G gives such specificity. The suppression of persistent current by ankyrin G seems to be mediated by direct binding of Nav1.6 to ankyrin G, since deletion of ankyrin-binding consensus sequence of Nav1.6 reduced the modification of inactivation by ankyrin G. These results raise an intriguing possibility that ankyrin-dependent gating of sodium channel might account in part for functional diversities or pathophysiological abnormalities of brain Nav channels. [Jpn J Physiol 54 Suppl:S134 (2004)]
