AngⅡ对人心房肌细胞膜钾通道电流影响及替米沙坦拮抗作用.doc

AngⅡ对人心房肌细胞膜钾通道电流影响及替米沙坦拮抗作用 　 作者：张殿新，黄岚，王海昌，张荣庆，程何祥，刘兵，张清，郭文怡 【关键词】 膜片钳术 　　【Abstract】AIM： To observe the effects of angiotensin Ⅱ (AngⅡ) on potassium currents of human atrial myocytes so as to reveal the mechanisms of atrial arrhythmia induced by AngⅡ, and to provide a laboratory basis for the application of angiotensin Ⅱ receptor antagonist in the treatment of atrial arrhythmias. METHODS: Single human atrial myocyte was isolated and the conventional wholecell configuration of patchclamp technique was used to detect membrane Ik1 and Ito. The experiment was conducted in four groups: control group, AngⅡ group, telmisartan group, and AngⅡ + telmisartan group. RESULTS: Compared with the control group, AngⅡ of 0.1 μmol/L significantly decreased the peak density of Ito in human atrial myocytes (pA/pF,6.55±0.52 vs 12.65±1.06 , Plt;0.01). Under the voltage of -100 mV, AngⅡ significantly increased the peak density of IK1 (pA/pF, -9.31±1.02 vs -5.23±0.98 , Plt;0.01). Telmisartan of 0.01 μmol/L had no significant effect on Ik1 and Ito in human atrial myocytes, but it antagonized the effects of AngⅡ. In AngⅡ + telmisartan group, the peak density of Ito (pA/pF, 11.74±1.28) and the peak density of IK1 ( pA/pF, -6.13±1.15) were both significantly different with those in AngⅡ group（Plt; 0.01）. CONCLUSION: AngⅡ has significant electrophysiological effects on human atrial myocytes. AngⅡ of 0.1 μmol/L significantly increases the peak density of IK1, but decreases the peak density of Ito in human atrial myocytes. Telmisartan antagonizes the effects of AngⅡ on human atrial myocytes. 　　【Keywords】 telmisartan; potassium channels; patch clamp techrieques; heart atria; muscle cells; angiotensinⅡ 　　【摘要】目的： 观察AngⅡ对人心房肌细胞膜钾电流的作用，揭示其参与房性心律失常的电生理机制，为应用AngⅡ受体拮抗剂治疗房性心律失常提供实验基础.方法： 急性分离单个人心房肌细胞，采用全细胞膜片钳方法记录内向整流钾电流(Ik1)、短暂外向钾电流（Ito）.实验分4组：对照组，AngⅡ（01 μmol/L）组，替米沙坦（001 μmol/L）组，AngⅡ+替米沙坦组.结果： 与对照组相比，01 μmol/L AngⅡ使人心房肌细胞膜Ito峰值电流密度明显下降(pA/pF, 655±052 vs 1265±106，P＜001）, 在-100ｍＶ电压下使IK1 峰值电流密度显著升高 (pA