Voltage-sensitive sodium channels: an evolving molecular view

Abstract

Sodium channel proteins have now been isolated from a number of nerve and muscle preparations. All are characterized by the presence of a very large glycoprotein subunit of approximately 260 kilodaltons which may contain the structural features required for voltage-dependent channel gating and cation selectivity. These purified proteins have been reconstituted into vesicle systems and planar bilayers and demonstrate the ensemble and single-channel behavior characteristic of the native sodium channel. Although the sodium channel from eel appears to consist of only the 260-kilodalton protein, the channels from rat brain and rat or rabbit skeletal muscle contain one or more smaller subunits of 37-39 kilodaltons. In skeletal muscle, a 38-kilodalton subunit is present in both conventionally purified channel and channel isolated with immunoaffinity techniques. The stoichiometry of the large (alpha) and the small (beta) subunits appears to be 1:1 in skeletal muscle but 1:2 in rat brain. The role of the small subunits in the normal functioning of the sodium channel remains to be defined.