Alterations in sodium channel gating produced by the venom of the marine mollusc Conus striatus.

The action of the venom from the marine mollusc Conus striatus was studied using the voltage-clamp technique on myelinated nerve. Conus venom applied to an isolated node of Ranvier at 1.1 micrograms protein/ml produced repetitive firing of action potentials when the node was depolarized under current-clamp conditions. Venom application produced a leftword (depolarizing) shift in both the peak sodium current-voltage and the permeability-voltage relationships. A concomitant decrease in maximum peak current and permeability also occurred. The time course of sodium current decline (inactivation) was slowed at all voltages by the presence of venom. Venom treatment caused only a slight depolarizing shift (5 mV) in the voltage-dependence of steady-state Na inactivation. The closing to the resting state of previously activated Na channels, "deactivation", was judged from Na "tail" currents following membrane repolarization, and was slowed more than four-fold by venom treatment. The changes in Na channel gating produced by Conus striatus venom can best be described as a stabilization of the open state of the Na channel and a shift in the voltage dependence of the opening of Na channels. The slowing of both inactivation and deactivation of Na channels can be simulated by alterations in the rate constants of a five state Markov model.