阿米洛利对心肌复极的影响及离子机制研究

Effects and ionic mechanisms of Amiloride on repolarization in myocytes

目的 :研究阿米洛利 (Amiloride)对心肌复极的影响及离子机制。方法 :用标准微电极技术记录阿米洛利对豚鼠乳头状肌细胞动作电位的影响 ;用膜片钳技术记录电压依赖性的钾电流。结果 :10 μmol/L、10 0 μmol/LAmiloride均可降低豚鼠乳头状肌动作电位幅度 ,延长动作电位时程 ;当累积浓度达 10 0 μmol/L时 ,Amiloride轻微抑制快激活延迟整流钾电流 (Ikr) ,对慢激活延迟整流钾电流 (Iks)无影响。 (1～ 10 0 ) μmol/L的Amiloride浓度依赖性地抑制内向整流钾电流 (Ik1)。结论 :阿米洛利通过抑制电压依赖性的钾电流 ,延长复极以发挥抗心律失常的作用。

AIM:To study the effects and ionic mechanisms of Amiloride on r epolarization in myocytes. METHODS:Action potentials of papillary muscle in isolated guinea pig was measured through standard and ion-selective microelectrodes. Voltage-dependent potassium currents in isolated guinea pig ve ntricular myocytes were recorded by using the whole-cell patch clamp techniques . RESULTS:In papillary muscle preparation of isolated guinea pig, 10 μmol/L、100 μmol/L Amiloride prolonged 90% action potential duration (248 .8±17.5 ms of control to 270.0±14.7 ms and 317.2±29.3 ms). 100 μmol/L Amilo ride decreased action potential amplitude(120.6±7.1 mV vs 105.4±2.3 mV ),maximal velocity of phase 0 depolarization(218.6±8.9 V/S vs 162.4±7.0 V/S) and 20% action potential duration ( 101.4±11.6 ms vs 131.6±17 .3 ms). And resting potential depolarized slightly moved from (-79.0±1.8)mV to (-67.4±5.3)mV. Administrated up to 100 μmol/L in an accumulative manner, Amiloride slightly depressed I kr. It had no effect on I ks. Amilorid e(1～100 μmol/L) depressed I k1 in a concentration-dependent manner. CONCLUSION:Amiloride prolonged duration of repolarization, depresse d potassium currents,which could give support to its uses in antiarrhythmia.