Mutation of Tyr401 to Cys in the skeletal muscle sodium channel rendered it highly susceptible to cadmium blockage but resistant to TTX, localizing the binding site within the pore.
Identifies the molecular position of a critical ion-binding site within the mammalian sodium channel pore.
Sodium channels are the major proteins that underlie excitability in nerve, heart, and skeletal muscle. Chemical reaction rate theory was used to analyze the blockage of single wild-type and mutant sodium channels by cadmium ions. The affinity of cadmium for the native tetrodotoxin (TTX)-resistant cardiac channel was much higher than its affinity for the TTX-sensitive skeletal muscle isoform of the channel (microliters). Mutation of Tyr401 to Cys, the corresponding residue in the cardiac sequence, rendered microliters highly susceptible to cadmium blockage but resistant to TTX. The binding site was localized approximately 20% of the distance down the electrical field, thus defining the position of a critical residue within the sodium channel pore.
Backx et al. (Fri,) reported a other. Mutation of Tyr401 to Cys vs. Wild-type skeletal muscle sodium channel was evaluated on Cadmium blockage and tetrodotoxin (TTX) resistance. Mutation of Tyr401 to Cys in the skeletal muscle sodium channel rendered it highly susceptible to cadmium blockage but resistant to TTX, localizing the binding site within the pore.