MOLECULAR-BASIS OF CHARGE MOVEMENT IN VOLTAGE-GATED SODIUM-CHANNELS

Voltage-dependent movement of a sodium channel S4 segment was examined by cysteine scanning mutagenesis and testing accessibility of the res idues to hydrophilic cysteine-modifying reagents. These experiments in dicate that 2 charged S4 residues move completely from an internally a ccessible to an externally accessible location in response to depolari zation by passage through a short ''channel'' in the protein. The ener getic problems of S4 movement have thus been solved in the same way th at many ion channels achieve highly selective and rapid ion permeation through an open pore, by restricting the contact region between the p ermion and its channel.