Clustering of voltage gated sodium channel in various excitable membranes.

Abstract

In excitable membranes, clustering of voltage gated sodium channels (VGSC) serves to enhance excitability at critical sites. The two most profoundly studied sites of channel clustering are the axon initial segment (AIS), where action potentials are generated and the node of Ranvier (NOR), where action potentials propagate along myelinated axons. Clustering of VGSC is found, however, in other highly excitable sites such as axonal terminals, post synaptic membranes of dendrites and muscle fibers, and pre-myelinated\xa0axons. In this review, different examples of axonal as well as non-axonal clustering\xa0of VGSC are discussed, and the underlying mechanisms are compared. Whether the clustering of channels is intrinsically- or extrinsically-induced, it depends on the submembranous actin-based cytoskeleton that organizes these highly specialized membrane microdomains through specific adaptor proteins.