Brief Communication Quinidine Delays IK Activation in Guinea Pig Ventricular Myocytes

A major action of the antiarrhythmic agent quinidine is prolongation of cardiac repolarization. In these experiments, the time-dependent effects of quinidine on the delayed rectifier potassium current, I,, a current contributing to cardiac repolarization, were investigated in acutely disaggregated guinea pig ventricular myocytes using the whole-cell recording configuration of the patch-clamp method. The effect of quinidine on I, was dependent on the duration of depolarization. After long (2,000 msec) pulses, IK was reduced by 30 ±27% (SD; n = 8, paired) by 10 P.M quinidine; in contrast, after short (100 msec) pulses, the drug decreased IK 65 ±35% (p<0.05). This effect was found both in paired experiments as well as when quinidine-pretreated cells were compared to non-pretreated cells. Quinidine significantly delayed IK activation (9 ± 20 msec at baseline vs. 44 ± 25 msec in drug, p< 0.05), but did not alter the subsequent time course of activation (time constant 659 ±118 msec). These findings are consistent with the hypothesis that quinidine promotes occupancy of a channel state from which opening does not occur. (Circulation Research 1988;62:1055-1058)