QUINIDINE-INDUCED OPEN-CHANNEL BLOCK OF K+ CURRENT IN RAT VENTRICLE

1 The effects of quinidine on calcium-independent outward K+ currents in rat ventricular myocytes were studied using whole-cell patch clamp techniques. 2 Quinidine sulphate (6 mu M) significantly prolonged repo larization of the ventricular action potential. This effect was larger during early repolarization (25% level) than at later times (90% leve l). 3 Quinidine reduced the amplitude of a transient outward current, and accelerated its rate of decay by approximately 4 fold at membrane potentials between 0 to +50 mV. Quinidine also reduced the amplitude o f a slowly inactivating, tetraethylammonium-sensitive 'pedestal' compo nent of the outward current. 4 The quinidine-induced block of the tran sient outward current was dependent on time and membrane potential. Ma ximal block occurred with depolarizations of about 100 ms duration, an d longer depolarizations (up to 1.5 s) produced little additional bloc k. The membrane potential dependence of quinidine-induced block was ve ry similar to the membrane potential dependence of activation of the t ransient outward current. The membrane potential dependence of steady- state inactivation of the transient outward current was not significan tly affected by quinidine. 5 These results show that quinidine blocks outward K+ currents in rat ventricular cells. The time and potential d ependence of this block suggests that quinidine blocks the transient o utward K+ current by acting primarily on the open state of these chann els.