严重烫伤延长大鼠心室肌细胞动作电位时程及其机制.pdfVIP

生理学报 Acta Physiologica Sinica, June 25, 2007, 59 (3): 375-381 375 研究论文 严重烫伤延长大鼠心室肌细胞动作电位时程的机制 邓建新，刘杰* 南方医科大学病理生理学教研室，广东省休克微循环重点实验室，广州 510515 摘 要：严重烫伤引起心肌细胞动作电位时程(action potential duration, APD)延长，通过加重烫伤心肌细胞钙紊乱和诱发室 性心律失常，促进烫伤心功能障碍的发生，但APD 延长的机制尚不清楚。通过制作约40% 体表面积(total body surface area, TBSA) III 度烫伤大鼠模型，在伤后12 h 大鼠心功能明显减弱时分离其心肌细胞，采用膜片钳技术观察心肌细胞APD 以及 动作电位复极化相关的重要离子通道电流，包括瞬间外向钾电流(transient outward K+ current, Ito) ，L- 型钙电流(L-type Ca2+ current, ICa-L)和内向整流钾电流(inward rectifier K+ current, IK1) 。结果显示，烫伤后12 h 单个心肌细胞APD 明显延长，APD50 和APD90 在烫伤组分别为(46.02±3.78) ms 、(123.24±12.48) ms (n=19) ，明显长于对照组的(23.28±4.85) ms 、(72.12±3.57) ms (n=17)(P 0.01) 。烫伤引起Ito 电流密度降低，+60 mV 下烫伤组的电流密度(20.39±1.98) pA/pF (n=25) 明显低于对照组的 (34.15±3.78) pA/pF (n=20, P 0.01); 烫伤组在−120 至−80 mV 电压刺激下所产生的IK1 电流密度显著低于对照组；而两组之间 I Ca-L 电流密度、电压依赖性的激活和失活无显著性差异。结果提示，烫伤引起心肌细胞APD 延长的机制与瞬间外向钾通 道和内向整流钾通道功能下调有关。 关键词：烫伤；动作电位；瞬间外向钾电流；内向整流钾电流；L - 型钙通道 中图分类号：R 6 4 4 Underlying mechanism for prolongation of action potential duration in ventricular cardiomyocytes of rats suffered from thermal injury DENG Jian-Xin, LIU Jie* Department of Pathophysiology, Key Laboratory of Shock and Microcirculation of Guangdong Province, Southern Medical University, Guangzhou 510515, China Abstract: Severe thermal injury causes prolongation of action potential duration (APD) in cardiomyocytes, which results in cardiac dysfunction by inducing disturbance of calcium dyshomeostasis in cardiac myocytes. However, the underlying mechanism for APD prolongation remains unclear. In the present study, we examined the major action potential repolarization-related ion channel currents in rat ventricular cardiomyocytes, including transient outward potassium current (Ito), inward rectifier potassium current (IK1) and L- 2+ type Ca current (ICa-L) to investigate the alterations of these currents, which might account for the pathogenesis of APD pr