Voltage-gated sodium and calcium channels in nerve, muscle, and heart

Voltage-gated ion channels are membrane proteins which underlie rapid electrical signals among neurons and the spread of excitation in skeletal muscle and heart. We outline some recent advances in the study of voltage-sensitive sodium and calcium channels. Investigations are providing insight into the changes in molecular conformation associated with open-closed gating of the channels, the mechanisms by which they allow only specific ion species to pass through and carry an electric current, and the pathological consequences of small perturbations in channel structure which result from genetic mutations. Determination of three-dimensional structures, coupled with molecular manipulations by site-directed mutagenesis, and parallel electrophysiological analyses of currents through the ion channels, are providing an understanding of the roles and function of these channels at an unprecedented level of molecular detail. Crucial to these advances are studies of bacterial homologues of ion channels from man and other eukaryotes, and the use of naturally occurring peptide toxins which target different ion channel types with exquisite specificity.