Abstract: AimTo clarify mechanisms that the antiarrhythmic effects of matrine and berbamine are weaker than those of amiodarone and RP58866. MethodsExperimental arrhythmic models were induced by aconitine, coronary artery ligation and electric stimulation in rats and rabbits. Whole-cell patch-clamp techniques were used to record I_K1, I_Kr, I_Ks and I_to. ResultsMatrine and berbamine significantly increased the dose of aconitine for induction of ventricular premature and ventricular tachycardia in rats, decreased the number of arrhythmias induced by coronary artery ligation in rats and increased ventricular fibrillation threshold (VFT) induced by electric stimulation in rabbits, but the anti-arrhythmic potency of matrine and berbamine was lower than that of amiodarone and RP58866. The inhibitory actions of matrine and berbamine on I_K1, I_Kr, I_Ks, I_to were lower than those of amiodarone and RP58866. The IC₅₀ of matrine for I_K1, I_Kr, I_Ks, I_towere (46±3), (32.9±1.2), (37±8) and (7.6±0.5) mol·L^-1, respectively. The IC₅₀ of amiodarone for I_K1, I_Kr, I_Ks, I_towere (21±5), (3.7±0.7), (5.9±0.9) and (5.9±0.6) mol·L^-1, respectively. ConclusionThe inhibitory actions of matrine and berbamine on I_K1, I_Kr, I_Ks, I_to were lower than those of amiodarone and RP58866, which might be the reason that the antiarrhythmic effects of matrine and berbamine were weaker than those of amiodarone and RP58866.