The scorpion alpha-like toxin Lqh III specifically alters sodium channel inactivation in frog myelinated axons.

Abstract

The effects of 1-100 nM Lqh III, an alpha-like toxin isolated from the scorpion Leiurus quinquestriatus hebraeus, were assessed on the nodal membrane potential and ionic currents of single frog myelinated axons. In current-clamped axons, Lqh III increased the duration of action potentials without markedly affecting the peak amplitude and the resting membrane potential. The toxin was less effective when the resting membrane potential of axons was increasingly more positive. The Lqh III-induced increase in action potential duration was not due to the blockade of K(+) channels, since the toxin had no significant effect upon the K(+) current. In contrast, Lqh III inhibited the inactivation of a fraction of the Na(+) current, leading to a maintained late inward Na(+) current which represented about 45% of the peak Na(+) current, as observed during long-lasting depolarisations and in steady-state Na(+) current inactivation-voltage relationships when the pre-pulse potential was more positive than about -30mV. The activation kinetics of the late Na(+) current were well described by a single exponential whose time constant was 8.53+/-0.78 ms (n=3). Finally, Lqh III slowed the time-course of the remaining peak Na(+) current inactivation by altering initial amplitudes (to time zero of depolarisation) and time constants of its fast and slow phases. No significant additional effect was detected during the action of the toxin. In conclusion, we propose that, in frog myelinated axons, the effects of Lqh III are those typically attributed to classical scorpion alpha-toxins.