Effects of toxins VI and VII from the scorpionCentruroides sculpturatus on the Na currents of the frog node of Ranvier

Abstract

New toxins, VI and VII, were purified from the venom of the North American scorpion, Centruroides sculpturatus, and studied in the voltage-clamped frog node of Ranvier. These toxins reduced peak inward Na currents and caused a transient, depolarization-induced shift in the voltage dependence of Na activation. Their effects were indistinguishable from those of toxins I, III and IV, as previously described by Meves et al. (1982). Toxin VII, 0.2 microgram/ml, shifted the voltage dependence of steady-state inactivation (h infinity). In four fibers, the mean shift of the h infinity (E) curve was -17 mV, compared to a mean shift of -28 mV in the descending branch of the INa(E) curve. The h infinity (E) curve with toxin VII was monotonic and inactivation was incomplete at positive potentials. Decreasing the pH from 7.4 to 5.7 increased the shift in the voltage dependence of activation with toxin. The increase with toxin VI at pH 5.7 was reversible on returning to pH 7.4, but the increase with toxin VII was not. The lack of reversibility of the effect of pH with toxin VII was quantified in two ways: the mean value of INa (measured at -62 mV with a conditioning pulse) at pH 7.4 was 5.1 times larger after treatment than before treatment with 0.1 microgram/ml of toxin VII at pH 5.7; the average concentration of toxin VII required for a shift of -30 mV at pH 7.4 was decreased by a factor of 4.3, to 0.19 microgram/ml (26 nM), by pretreatment at pH 5.7.(ABSTRACT TRUNCATED AT 250 WORDS)