利多卡因对离体大鼠心室肌细胞内向整流钾电流的影响

Effect of Lidocaine on Inward Rectifier Potassium Currents in Isolated Rat Ventricular Myocytes

目的研究利多卡因对大鼠心室肌细胞内向整流钾电流的影响,探讨局麻药毒性反应中利多卡因导致心率变慢是否与抑制Ikl有关。方法酶消化法急性分离大鼠心室肌细胞,采用全细胞膜片钳技术,记录不同浓度利多卡因对大鼠心室肌细胞内向整流钾电流的影响并做出浓度效应曲线,求得其半数抑制浓度。结果保持电压-40 mV,钳制电压-120 mV条件下,局麻药毒性反应浓度的利多卡因100μmot／L使Ikl的电流幅值降低(21．1±7．4)％(P<0．05),但不改变Ikl翻转电压以及电流-电压曲线的形状;冲洗后,Ikl能够完全恢复。500,1000,5000μmoL／L的利多卡因抑制Ikl电流呈浓度依赖性,电流抑制率分别为(32．4±5．7)％,(71．8±8．9)％,(84．5±4．9)％,其IC50为1426．4μmoL／L。结论局麻药毒性反应中,利多卡因呈浓度依赖性抑制大鼠心室肌细胞Ikl,可能延长动作电位时程导致心率变慢。

Objective To study the influence of lidocaine on inward rectifier potassium currents （ Ⅰk1 ） in ventricular myocytes of rats, in order to investigate whether the anesthetic toxicity reaction of lidocaine is related to inward rectifier potassium currents. Methods Adult Wistar rats of both sexes were anesthetized with pentobarbital. The hearts were removed and ventricular myocytes were prepared. Whole-cell patch clamp technique was used to study Ⅰk1 in isolated rat ventricular myocytes. The changes in Ⅰk1 produced by 1001μmol/L with different holding potentials or by different concentrations of lidocaine with holding potential of - 120mV were analyzed. Results Lidocaine 1001μmol/L inhibited the Ⅰk1 without any significant effects on reverse potential （ -50 - -60mV） and the shape of the I-V curve. Inward rectifier potassium currents were concentration-dependently inhibited by lidocaine of 500,1 000,5 0001μmol/L. The inhibitive rates of currents were（ 32.4 ± 5.7 ） % , （ 71.8 ± 8.9 ） % , （ 84.5 ± 4.9 ） % respectively, and the mean IC50 value was 1426.41μmol/L. Conclusion In anesthetic toxicity reaction, lidocaine significantly inhibits Ⅰk1 in isolated rat ventricular myocyte. This may explain the prolonged duration of action potential of ventricular myocyte produced by lidocaine.