AIM: To study the effects of berberine on inward rectifier potassium current (Ik1) and outward delayed rectifier potassium current (Ik) of guinea pig ventricular my ocytes, and on human ether-a-go-go related gent (HERG) channel expressed in Xenopus oocytes. METHODS: Whole cell patch-clamp and geneclamp techniques were used to record ionic currents.RESUTS: Berberine prolonged action potential duration (APD) and inhibited Ik1 and Ik in a concentration-dependent manner. Berberine 100μmo1/L increased APD90 from (450±48) ms to (888±90) ms (n=6,P<0.01), and inhibited Ik1 by 64%±7%(n=6,P<0.01). Berberine 50μmo1/L inhibited Ik by 57%±6%,Iktmil by 52%±6%(n=6,P<0.01). Berberine produced a voltage-dependent block on Ik that increased with stronger depolarization, and once all channels activated, there was no further block at positive potentials. Berberine blocked the HERG channels potently with an IC50 value of approximately 75μmo1/L. This block was voltage-dependent, suggesting that it probably bind to either open or inactivated HERG channels. CONCLUSION: Berberine prolonged APD and possessed blocking effect on Ik1,Ik, and HERG channel expressed in Xenopus oocytes. The antiarrhythmic mechanism of berberine is related to its inhibitory effects on Ik1,Ik,and HERG channel.