阿米洛利对心肌自律性的影响及其机制

Effects and mechanism of amiloride on the autorhythmia of cardiac myocytes

目的 :研究阿米洛利 (amiloride)对心肌自律性的作用及其电生理机制。方法 :用培养乳鼠心肌细胞观察阿米洛利对心肌细胞搏动频率的影响 ;用标准微电极技术记录阿米洛利对家兔窦房结动作电位的作用 ;用膜片钳技术记录电压依赖性的钙通道电流。结果 :10 0 μmol/L阿米洛利可使培养心肌细胞收缩频率减慢 ;10 0 μmol/L阿米洛利还可降低窦房结起搏细胞最大除极化速率 ,使静息电位轻度正移。阿米洛利在 10～ 10 0 μmol/L范围内抑制L型及T型钙通道电流。结论 :阿米洛利可抑制心肌L、T型钙通道电流 ,抑制窦房结自动除极过程 。

Objective To explore the effects and electrophysiological mechanisms of amiloride on the autorhythmia of cardiac myocytes. Methods Contractility rate of cultured myocytes of neonatal rat was measured by image system. Action potentials in sinoatrial node from rabbits were examined using standard microelectrodes. L and T-type calcium currents in isolated guinea pig ventricular myocytes were recorded by using the whole-cell patch clamp techniques. Results 100 μmol/L amiloride slowed down the contractility rate of myocytes. 10 μmol/L amiloride prolonged 50% action potential duration [(119.6±6.7) vs (127.6±9.4) ms], decreased rate of diastolic depolarization [(0.51±0.01) vs (0.36±0.02) V/S], prolonged spontaneous cycle length [(525.3±14.8) vs (662.5±8.9) ms] in sinoatrial node. 10 and 100 μmol/L amiloride depressed amplitude of L-type calcium current, but did not change the shape of its I-V curve. 100 μmol/L amiloride depressed T-type calcium current. The effect was not frequency-dependent. Conclusions Amiloride depressed L and T-type calcium current, inhibited the auto-rhythm of sinoatrial node, decreased contractility rate of myocytes, which resulted in its antiarrhythmic effect.