Inhibitory effects of berberine on I-K1, I-K, and HERG channels of cardiacmyocytes

AIM: To study the effects of berberine on inward rectifier potassium curren t ( I-Kl) and outward delayed rectifier potassium current (I-K) Of guinea p ig ventricular myocytes, and on human ether-a-go-go related gene (HERG) cha nnel expressed in Xenopus oocytes. METHODS: Whole cell patch-clamp and gene clamp techniques were used to record ionic currents. RESULTS: Berberine pro longed action potential duration (APD) and inhibited I-Kl and I-K in a conc entration-dependent manner. Berberine 100 mu mol/L increased APD(90) from ( 450 +/- 48) ms to (888 +/- 90) ms (n = 6, P <0.01), and inhibited I-Kl by 6 5% +/- 7% (n =6, P <0.01). Berberine 50 mu mol/L inhibited I-K by 57% +/- 6 %, I-Ktail by 53% +/- 6% (n = 6, P < 0.01). Berberine produced a voltage-de pendent block on IK that increased with stronger depolarization, and once a ll channels were activated, there was no further block at positive potentia ls. Berberine blocked the HERG channels potently with an IC50 value of appr oximately 75 <mu>mol/L. This block was voltage-dependent, suggesting that i t probably bind to either open or inactivated HERG channels. CONCLUSION: Be rberine prolonged APD and possessed blocking effect on I-Kl, I-K, and HERG channel expressed in Xenopus oocytes. The antiarrhythmic mechanism of berbe rine is related to its inhibitory effects on I-Kl, I-K, and HERG channel.