Cadmium-induced blockade of the cardiac fast Na channels in calf Purkinje fibres

Abstract

The fast transient inward current elicited by depolarizations above about -60 mV in calf Purkinje fibers was depressed by Cd in concentrations < 1 mM. The Cd-sensitive current, which strongly depended on external Na, was recorded in the presence of 2 mM MnCl2 and was blocked by TTX [tetrodotoxin], indicating that a contamination from slow Ca-dependent currents could be discounted. The current reduction caused by Cd was also observed in nominally Ca-free solutions. The Cd-induced depression of the fast Na current was not accompanied by changes in the current kinetic parameters, as revealed by comparing inactivation curves and peak current voltage relations at different Cd concentrations, and could be attributed to a voltage-independent channel blocking action. Half-blockade occurred at 0.182 .+-. 0.06 mM (n = 4). Plots of peak current amplitude as a function of the Cd concentration showed that the cooperation of 2 Cd ions was required to block a single channel.