ANTIARRHYTHMIC AND BRADYCARDIAC DRUGS INHIBIT CURRENTS OF CLONED K+ CHANNELS, K-V1.2 AND K-V1.4

We investigated the effects of the antiarrhythmic drugs, quinidine, disopyramide, flecainide, clofilium, verapamil, and the bradycardic drug, bertosamil, on the currents of the cloned K+ channels, K-V1.2 (I-K(V1.2)) and K-V1.4 (I-K(V1.4)), using the Xenopus oocyte expression system. Both I-K(V1.2) and I-K(V1.4) were inhibited in a concentration-dependent manner by quinidine (10 mu M to 1 mM), flecainide (10 mu M to 1 mM), clofilium (10-300 mu M), verapamil (10 mu M to 1 mM) and bertosamil (10 mu M to 1 mM) but not by disopyramide (10 mu M to 1 mM). The inhibitory effects of clofilium, verapamil and bertosamil on I-K(V1.2) were time-dependent. The decay time course of I-K(V1.4) was accelerated by clofilium, verapamil and bertosamil, but decelerated by quinidine and flecainide. These results indicate that I-K(V1.2) and I-K(V1.4) are targets for the four antiarrhythmic drugs and the bradycardic drug.