INCREASE IN ACTION-POTENTIAL DURATION AND INHIBITION OF THE DELAYED RECTIFIER OUTWARD CURRENT I-K BY BERBERINE IN CAT VENTRICULAR MYOCYTES

1 In the present work, the effects of the antiarrhythmic drug, berberi ne, on action potential and ionic currents of cat ventricular myocytes were studied. 2 Berberine prolonged action potential duration in cat ventricular myocytes without altering other variables of the action po tential. 3 The drug at concentrations of 0.3-30 mu M blocked only the delayed rectifier (I-K) current with an for IC50=4.1 mu M. Berberine p roduced a tonic block and a phasic block that was increased with the d uration of the depolarizing pulse. The blocking effect on I-K was use- dependent. but not frequency-dependent. 4 In cardiac preparations two delayed rectifier currents have been found: a rapid (I-Kt) current and a sloe (I-Ks) current. In the present work it has been Found that ber berine at the concentrations used. selectively blocked I-Kr. 5 At conc entrations higher than 10 mu M it also decreased the transient outward (I-tol) current. The drug did nor have effects on the inward rectifie r (I-Kl) or the high threshold calcium current (I-Ca-L) 6 These result s show that berberine is a specific potassium channel blocker. The inc rease in action potential duration induced by berberine can be explain ed mainly by its blocking effects on I-K.