MODULATION OF THE DELAYED RECTIFIER, IK, BY CADMIUM IN CAT VENTRICULAR MYOCYTES

The effects of cadmium on the delayed outward potassium current (I(K)) were investigated in isolated cat ventricular myocytes using the single suction pipette voltage-clamp technique. I(K) activation was examined using peak tail currents elicited after 750-ms voltage-clamp steps to selected membrane potentials from a holding potential of -40 mV. In the presence of Cd2+ (0.2 mM), peak tail currents increased from a control value of 85 +/- 12 to 125 +/- 18 pA (n = 4). Activation curves constructed from the average peak tail-current measurements in all experiments showed that Cd2+ shifted the voltage dependence of activation to more positive potentials by 16.4 +/- 2.0 mV and increased the slope factor of the activation curve from 6.1 +/- 0.2 to 6.9 +/- 0.2 mV. In the absence of Cd2+, increases in holding potential from -30 to -70 mV had no effect on the magnitude of the peak tail currents, suggesting that the Cd2+-induced increase was not the result of a voltage-dependent increase in the number of available K+ channels at the holding potential. Slow voltage ramps from -70 to +70 mV revealed that Cd2+ increased the outward current at membrane potentials positive to +20 mV and shifted the voltage range in which I(K) inwardly rectified to more positive potentials. The fully activated current-voltage relationship was also shifted to more positive potentials by Cd2+. Cd2+ did not alter channel selectivity for K+. The results cannot be entirely explained by simple surface potential theory whereby nonspecific screening of uniformly distributed fixed negative surface charges on the membrane by divalent ions gives rise to apparent shifts in the voltage dependence of channel activation, but suggest that Cd2+ is, in addition, acting more specifically at a site on or near the K+ channel.