严重烫伤延长大鼠心室肌细胞动作电位时程的机制  

Underlying mechanism for prolongation of action potential duration in ventricular cardiomyocytes of rats suffered from thermal injury

作　　者：邓建新[1] 刘杰[1] 

机构地区：[1]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

出　　处：《生理学报》2007年第3期375-381,共7页Acta Physiologica Sinica

基　　金：the National Natural Science Foundation of China(No.30570418;30570940)

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12h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12h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,+60mV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?80mV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ICa-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。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-type Ca^2 current （ICa-L） to investigate the alterations of these currents, which might account for the pathogenesis of APD prolongation induced by thermal injury. Twelve hours after approximately 40% of the total body surface area, full-thickness （third-degree） cutaneous thermal injury was produced in rats, ventricular cardiomyocytes were isolated from the hearts with systolic and diastolic dysfunction. APD was found to be markedly prolonged, while APD50 and APD90 in ventricular cardiomyocytes from rats with thermal injury were （46.02±3.78） ms and （123.24±12.48） ms （n=lg）, respectively, significantly longer than （23.28±4.85） ms and （72.12±3.57） ms （n=17, P〈0.01） in ventricular cardiomyocytes from sham rats. Thermal injury remarkably suppressed Ito density in ventricular cardiomyocytes.Ito density at ＋60 mV was decreased from （34.15±3.78） pA/pF （n=20） in sham group to （20.39± 1.98） pA/pF （n=25, P〈0.01） in thermal injury group, and the decrease extended from -30 to ＋60 mV. Similarly, current densities of IK1 from -120 to -80 mV in thermal injury group were also significantly lower than that in sham group. In contrast, we failed to detect any alterations in ICa-L density, and voltage-dependence of activation and inactivation in thermal injury group, compared with that in sham group. Taken together, our data suggest that thermal injury results in function downregulation of transient outward potassium channels and inwardrectifier potassiu

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 

分 类 号：R644[医药卫生—外科学]