Action potentials in mammalian nerve and muscle are generated by a stereotyped sequence of alterations in membrane conductance to monovalent cations [ 1,2]. The fundamental change that leads to the initiation of an action potential is a regenerative, but self-limited, increase in membrane conductance to sodium ions [3]. This timeand voltage-dependent conductance pathway is controlled by a unique transmembrane protein, the voltage-sensitive sodium channel [4].
Detailed kinetic analysis of currents flowing through the sodium channel began more than 30 years ago with the pioneering work of Hodghn and Huxley [3]. Biochemical characterization of this channel protein was undertaken more recently but has moved forward rapidly with concurrent advances in general membrane biochemistry. It is now possible to isolate the sodium channel protein from nerve and muscle membranes [5-71, to examine its molecular properties [8lo], and to reconstitute it into defined lipid vesicles [11][12][13].
In this report, the molecular properties of the voltage-sensitive sodium channel purified from mammalian skeletal muscle will be reviewed and the evidence for its functional integrity considered. Although this discussion will concentrate on recent progress that has been made with reconstitution of the sodium channel from skeletal muscle, reviews of biochemical approaches to sodium channels in general [ 141 and in rat brain in particular [ 151 have appeared elsewhere.
NEUROTOXINS AND SODIUM CHANNELS
Since the sodium channel has no natural ligands and performs no function in the absence of an intact membrane, identifying the solubilized channel protein can be a limiting factor in biochemical studies. Work with the channel, therefore, has relied heavily on its interaction with specific neurotoxins to locate this protein after its