Selective modification of the squid axon Na currents by Centruroides noxius toxin II-10

We have studied the effects of the purified toxin II-10, from the venom of the scorpion Centruroides noxius Hoffmann, on the Na and K currents of voltage clamped squid giant axons. Extracellular applications of 10 microM of toxin II-10 produced a selective depression of peak Na currents, with no significant effects on the time course of K currents. On pharmacologically separated Na currents, low concentrations of toxin II-10 (0.28-1 microM) caused a reversible decrease in inward and outward peak INa, with little effect on either the maintained level of the currents or their turning-off. At high concentrations (greater than 3 microM), toxin II-10 drastically reduced the peak conductance and increased both the level of the maintained conductance, and the time course of its turning-off. It is suggested that, when applied extracellularly on squid axons, toxin II-10 primarily reduces the peak Na conductance by modifying the activation of fast-inactivating Na channels. At high concentrations (10 microM), the toxin also modifies the rate constants of the transition from the inactivated to the second open state of the channel (Chandler and Meves, 1970) thus producing an increased level of the maintained Na conductance. It is also very likely, however, that peak conductance and maintained conductance reflect two separate populations of Na channels on which toxin II-10 has a differentiated action. Under these conditions, toxin II-10 would be the first reported toxin which can pharmacologically separate the two types of channels.