The effect of scorpion venoms on the sodium currents of the squid giant axon.

1. The effect of externally applied scorpion venoms (0.1--0.5 mg/ml., species Leiurus quinquestriatus and Centruroides sculpturatus) on the Na currents of intracellularly perfused squid giant axons has been studied with the voltage-clamp method. 2. The venoms from the two species had the same effect. They reduced the size of the peak conductance but had little effect on its kinetics (time to peak, time constant of inactivation) and on its steady-state inactivation. The venoms increased markedly, however, the maintained conductance and the time constants of its turning-on and turning-off. 3. The voltage dependence of the maintained conductance was determined (a) by fitting a modified Hodgkin--Huxley equation to the Na currents and (b) by measuring the tail currents at the end of depolarizing pulses. The maintained conductance rose with increasing depolarization from a minimum at -20 mV to a maximum at 40 mV. The peak conductance, by contrast, was constant in the positive potential range. 4. The ratio maintained conductance in venom to maintained conductance in control varied between 2 and 7 (depending on the venom concentration and the time of treatment) and was not significantly dependent on membrane potential. 5. Peak current and maintained current reversed sign at the same potential and were both blocked by tetrodotoxin. 6. During a pulse to -2 mV preceded by a pre-pulse to -42 mV the Na conductance showed a rapid initial increase followed by a slower decay and a subsequent slow increase, reflecting the activation and inactivation of the peak conductance and the slow development of the maintained conductance. 7. Many of the observations are compatible with the idea that scorpion venoms increase the number of channels which go from the peak conductance state into the maintained conductance state (open in equilibrium or formed from closed in equilibrium or formed from open transition of the inactivation gate, see Chandler & Meves (1970 a, b)). But the alternative hypothesis that peak conductance and maintained conductance reflect two separate populations of Na channels cannot be ruled out.