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盐酸小檗碱对甲状腺素性豚鼠心肌病心肌细胞中I Kr , IKsIK1的抑制作用

Inhibition of berberine on I Kr ,I Ks and I K1 in thyroxine induced cardiomyopathic guinea pig ventricular myocytes

  • 摘要: 目的 : 研究盐酸小檗碱(berberine,Ber)对甲状腺素性豚鼠心肌病中延迟整流外向钾电流中快激活成分(I Kr )和慢激活成分(I Ks )及内向整流电流(I K1)的抑制作用。 方法 : 豚鼠腹腔注射L-甲状腺素造成心肌病后,分离单个心肌细胞,用全细胞膜片钳技术记录钾电流。 结果 : 在心肌病细胞的I Kr ,I Ks 和IK1电流密度均明显增大,Ber 30 mmol/L分别抑制心肌病细胞I Kr 22.8%(+10 mV)和I Ks 29.5%(+80 mV),其对I Ks 的阻断作用大于I kr 。Ber 30 mmol/L也能阻断心肌病细胞I K129.1%(+120 mV),但不影响其反转电位。Ber(1~300 mmol/L)浓度依赖性地阻断心肌病细胞I Kr 及I Ks ,其IC50分别为76 mmol/L和55.37 mmol/L。 结论 : 甲状腺素性心肌病中出现异常增大的I Ks ,I Kr 及I K1离子流,Ber有明显阻断作用。

     

    Abstract: Aim :To study the effects of berberine(Ber) on the rapidly activating component(I Kr ),the slowly activating component(I Ks) of the delayed rectifier potassium current and the inward rectifier potassium current(I K1) in cardiomyopathic guinea pig ventricular myocytes. Methods :After guinea pigs were ip L-thyroxine 0.5 mg/kg for 10 d,their hearts were cardiomyopathic.Then whole cell patch-clamp recording technique was used to observe the effect of 30 μmol/L Ber on the I Kr ,I Ks and I K1in cardiomyopathic guinea pig ventricular myocytes. Results :In cardiomyopathic guinea pig ventricular myocytes,Ber 30 μmol/L markedly inhibited I Kr and I Ks by 22.8% and 29.5% at +10 mV and +80 mV,respectively.The effect of Ber on I Ks was greater than that on I Kr .Ber 30 μmol/L also inhibited the inward component of I K1 by 29.1% at+120 mV,but the reverse potential of I K1was unaffected.Ber(1- 300 μmol/L) was shown to inhibit I Kr and I Ks in a concentration-dependent manner.Their IC50 were 76.74 μmol/L and 55.37 μmol/L,respectively. Conclusion :Ber inhibited I Kr ,I Ks and I K1in cardiomyopathic guinea pig ventricular myocytes,which may be important in understanding the antiarrhythmic effects of this drug.