Pursuing the structure and function of voltage-gated channels.

A cyclical process of experimentation and theoretical analysis is being used to develop increasingly precise models of the structure and functional mechanisms of membrane proteins. Nucleic acid sequences have been determined for several voltage-gated sodium, calcium and potassium channels from invertebrates and vertebrates and from nerve and muscle tissues. Some of these sequences have been altered using site-directed mutagenesis. Properties of channels expressed after injection of normal and altered mRNA into Xenopus oocytes have been analysed by a variety of patch-clamp techniques. Preliminary structural models based on the first sequence information on sodium channels need to be modified to account for a large amount of new data. Here, Robert Guy and Franco Conti present their current view of the activation mechanism and ion selectivity of the voltage-gated channels.