Chemical modification of sodium channel inactivation: separate sites for the action of grayanotoxin and tetramethrin

The gating mechanisms of the sodium channel are known to be modified by grayanotoxin and the pyrethroid tetramethrin. Voltage clamp experiments with internally perfused squid giant axons were performed to determine whether or not these two chemicals shared a common site of action in exerting their effects. An additive effect of the two drugs in prolonging sodium currents was observed. Additionally, the characteristic tetramethrin-induced sodium tail current and the grayanotoxin-induced hyperpolarizing shift in the voltage that activated the sodium current were observed simultaneously and independently of the order of drug introduction. Inactive stereoisomers of tetramethrin, which are known to prevent the active tetramethrin stereoisomers from exerting their effect, had no effect on the development of the grayanotoxin-induced modifications of sodium current. It was concluded that tetramethrin and grayanotoxin act at separate sites of action in modifying the sodium channel gating mechanisms in the squid axon membrane.