Effect of Tityus gamma toxin on the activation process in sodium channels of frog myelinated nerve.

Recently it has been established that y toxin of Tityus serrulatus scorpion venom has a very high affinity to Na channels and can be successfully used as a marker during their purification from excitable membranes (Barhanin et al. 1983 ; Grishin 1983). There has, however, been some controversy concerning the effects of the y toxin on properties of Na channels in different tissues. Thus, in neuroblastoma cells the y toxin induces a shift in the voltage depencence of Na activation to more negative potentials, E (Barhanin et al. 1983). By contrast, in frog skeletal muscles the y toxin causes a partial block of Na channels with no changes in the voltage dependence or kinetics of sodium currents, JNa (Barhanin et al. 1984). In the present paper we give a short description of the effects of y toxin* on INa in frog node of Ranvier. Application of 0.15—0.30 umol/1 y toxin to voltag-clamped nodal membrane caused an irreversible reduction in the maximum Na conductance, gNa, accompanied by a negative shift in the voltage dependence of Na channels activation and a decrease in the slope of gNa—E curve. The voltage shift in Na + channels activation was transiently enhanced by strong depolarizing pulses, and decayed slowly (r = 20s at 5—6 °C) to its initial value. Fig. 1A illustrates toxin-induced changes in INa—E relation without ( • ) and with (A) conditioning pulsing to E = + 60 mV. In some experiments, the voltage shift of gfNa was absent before pulsing and it always appeared after conditioning depolarizing pulses (Fig. 1 B). The steepness factor, k, of the </Na—E curve (number of mV required to give an e-fold change of gNa) was increased by the toxin treatment combined with repetitive pulsing from = 7 to = 1 1 , indicating a reduction in the effective gating charge of the Na channel. The toxin did not abolish complete inactivation of the channels, and, as a rule, had no effect on the reversal potential after conditioning pulsing.