The effects of berberine on potassium channel subtypes were investigated by using patch-clamp whole cell recording techniques. Berberine is known to be effective in lowering blood glucose and ameliorating arrhythmia. Our results indicate that, berberine can prolong action potential duration (APD), decrease IK1 and outward Itail, but showed no effect on IK. In addition, berberine was also shown to antagonize cromakalim (BRL-34915) induced inhibition of APD and the increase of KATP. These suggest that berberine can inhibit voltage- dependent and ATP-sensitive potassium channels. It appears that the mechanisms of antiarrhythmic and antidiabetic action of berberine might be due to its potassium channel blocking effects.