Supersensitivity to tetrodotoxin and lignocaine of sea anemone toxin II-treated sodium channel in guinea-pig ventricular muscle.

1. Sea anemone toxin II (ATX II, 20-30 nM) doubled the action potential duration in guinea-pig papillary muscles without affecting the maximum rate of rise of the action potential (Vmax) and the resting potential. 2. Tetrodotoxin and lignocaine shortened the prolonged action potential in the ATX II-treated papillary muscles in concentrations (30 nM - 3 microM) at which these drugs did not suppress the Vmax. 3. Whole-cell voltage-clamp experiments with single ventricular cells showed that ATX II produced a slowly decaying inward sodium current following a transient sodium current upon depolarization. 4. The ATX II-induced slowly decaying current was reduced by tetrodotoxin or lignocaine in concentrations (300 nM-1 microM for tetrodotoxin, 3-10 microM for lignocaine) at which these drugs failed to affect the Vmax in cells not treated with ATX II. 5. These results suggest that sodium channel modification by ATX II not only changes its kinetics but also increases the susceptibility of the channel to block by tetrodotoxin and lignocaine.