Structure and Functional Reconstitution of the Voltage-sensitive Sodium Channel from Rat Brain

Electrophysiological experiments using the voltage-clamp technique have shown that the initial rapid de-polarization during an action potential in nerve, skeletal muscle, and heart muscle results from rapid voltage-dependent increases in membrane permeability o Na +. Many different lines of evidence indicate that selec-tive transmembrane Na § channel is responsible for the rapid Na § permeability increase during the action po-tential. Selective ion permeation is mediated by a hy-drophilic pore containing a Na+-selective ion coordina-tion site, designated the ion selectivity filter (Hille 1971, 1972). Ion conductance through the Na + channel is regulated, or gated, by two separate processes: ac-tivation, which controls the rate and voltage-depen-dence of the Na § permeability increase following de