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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.广东,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，I_(to)），L--型钙电流（L--type Ca~(2+) current，I_(Ca-L)）和内向整流钾电流（inward rectifier K~(+) current，I_(K_(1))）。结果显示，烫伤后12h单个心肌细胞APD明显延长，APD_(50)和APD_(90)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）（{sl P}<0.01）。烫伤引起，I_(to)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，{sl P}〈0.01）；烫伤组在--120至--80mV电压刺激下所产生的I_(K_(1))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

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

Deng Jianxin, Liu Jie

Department of Pathophysiology, Key Laboratory of Shock and Microcirculation of Guangdong Province, Southern Medical University.Guangzhou 510515,Guangdong

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 （I_(to)）, inward rectifier potassium current （I_(K_(1))） and L-type Ca~(2+) current （I_(Ca-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 APD_(50) and APD_(90) 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 I_(K_(1)) 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 I_(Ca-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 potassium channels, which contributes, at least in part, to APD prolongation and subsequent cardiac dysfunction.

Key words: thermal injury;Action potential;transient outward potassium current;inward rectifier potassium current;L-typecalcium channel

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引用本文：

邓建新, 刘杰. 严重烫伤延长大鼠心室肌细胞动作电位时程的机制[J]. 生理学报 2007; 59 (3): 375-381.

Deng Jianxin, Liu Jie. Underlying mechanism for prolongation of action potential duration in ventricular cardiomyocytes of rats suffered from thermal injury. Acta Physiol Sin 2007; 59 (3): 375-381 (in Chinese with English abstract).