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目的:研究小檗碱(Ber)对豚鼠心室肌细胞钾通道和动作电位作用,以及在蛙卵中表达的人的HERG通道的作用。方法:酶解方法分离单个心肌细胞,采用全细胞膜片箝方法记录钾离子电流及动作电位,基因箝技术研究HERG通道电流。结果:Ber可显著延长动作电位时程,并呈剂量依赖性。Ber 100μmol/L使APD_(90)由对照的(450±48)ms延长至(888±90)ms(n=6,P<0.01)。Ber对I_(Kl)及I_K呈剂量依赖性抑制作用。Ber 100μmol/L对I_(Kl)的抑制率达65％±7％(n=6,P<0.01)。Ber 50μmol/L对I_K的抑制率达57％±6％;对I_(Ktail)的抑制率达53％±6％。Ber对I_K作用呈现电压依赖性。Ber对在蛙卵中表达的HERG通道具有很强的阻断作用,IC_(50)为75μmol/L,此阻断作用也呈电压依赖性。结论:Ber可使动作电位时程明显延长,对I_(Kl)及I_K具有阻断作用。Ber可显著抑制HERG通道。Ber抗心律失常的机制与其抑制I_(Kl)、I_K及HERG通道密切相关。
AIM: To investigate the effects of berberine on potassium channels and action potentials in guinea pig ventricular myocytes and on human HERG channels expressed in frog eggs. Methods: Single cardiomyocytes were isolated by enzymolysis method. Potassium current and action potential were recorded by whole-cell patch-clamp technique. HERG channel current was studied by gene patch technique. Results: Ber significantly prolonged the action potential duration in a dose-dependent manner. Ber 100 μmol / L prolonged APD 90 from (450 ± 48) ms to (888 ± 90) ms from control (n = 6, P <0.01). Ber inhibited I_ (Kl) and I_K in a dose-dependent manner. The inhibition rate of Ber 100μmol / L to I_ (Kl) was 65% ± 7% (n = 6, P <0.01). Ber 50μmol / L of I_K inhibition rate of 57% ± 6%; I_ (Ktail) inhibition rate of 53% ± 6%. Ber has a voltage-dependent effect on I_K. Ber has a strong blocking effect on the HERG channel expressed in the frog eggs, with an IC 50 of 75 μmol / L and this blocking effect is also voltage-dependent. Conclusion: Ber can significantly prolong the action potential duration and block I_ (Kl) and I_K. Ber can significantly inhibit the HERG channel. The mechanism of Ber anti-arrhythmia is closely related to its inhibition of I_ (Kl), I_K and HERG channels.