Puerarin: a novel antagonist to inward rectifier potassium channel (IK1).

Puerarin, isolated from the root of pueraria, had been widely used to prevent and treat arrhythmia. We show that puerarin effectively prevents and reverses aconitine-induced arrhythmias in perfused heart in vitro and in rats in vivo. To study the mechanisms of antiarrhythmic action of puerarin, we investigated the electrophysiological actions of puerarin using whole-cell clamp in isolated rodent ventricular myocytes and two electrode voltage-clamp (TEV) in I(K1)-expressing Xenopus oocytes. Puerarin had no prominent effect on action potentials of ventricular myocytes from guinea pig. However, puerarin (1.2 mM) significantly inhibited the I(K1) current in rat ventricular cells. Consistently, puerarin blocked I(K1) expressed in Xenopus oocytes in a dose-dependent manner. Puerarin competed with barium, an open-channel blocker of I(K1), to inhibit I(K1) currents. Thus, our data demonstrated that puerarin is a novel open-channel blocker of I(K1), which may underlie the antiarrhythmic action of puerarin.