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, IK, 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 IK 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 microM quinidine; in contrast, after short (100 msec) pulses, the drug decreased IK 65 +/- 35% (p less than 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 less than 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.
D000818:Animals; D003864:Depression, Chemical; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology*; D007473:Ion Channels / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology*; D011690:Purkinje Fibers / Q000187:drug effects; D011802:Quinidine / Q000494:pharmacology*
D007473:Ion Channels; D011802:Quinidine