Modification of Na channel gating by an α scorpion toxin from Tityus serrulatus

Abstract

The effects of TslV-5, a toxin isolated from the Brazilian scorpion TiOrus serrulatus, on whole-cell and single-channel Na currents were determined in N 18 neuroblastoma cells. In whole-cell records at a test potential of -10 mV, external application of 500 nM TsIV-5 slowed inactivation 20-fold and increased peak current by about one-third without changing time-to-peak. Both the steadystate activation and inactivation curves were shifted to more negative potentials. Other α scorpion toxins produce similar effects but the single-channel mechanism is not known. TslV-5 caused a voltage-dependent prolongation of mean singlechannel open time such that at a test potential of -60 mV no change was observed, whereas at - 20 mV mean open time increased about threefold and prolonged bursting was observed. Macroscopic current reconstructed from summed single-channel records showed a characteristic toxin-induced potentiation of peak current and a 20-fold slowing of the decay phase. TsIV-5 does not discriminate between tissue-specific Na channel subtypes. Prolonged open times and bursting were also observed in toxin-treated Na channels from rat ventricular myocytes, rat cortical neurons, and mouse skeletal muscle. The toxin effects are shown to be consistent with a kinetic model in which TslV-5 selectively interferes with the ability of the channel to reach the inactivated state. © 1989, Rockefeller University Press., All rights reserved.