海葵毒素对心肌钠通道开放模式、动作电位及心电图QT间期的影响

李慈珍　 王红卫　 刘建立　 刘凯　 杨智日方　 刘远谋　

摘　要：应用膜片箝技术记录游离豚鼠心肌细胞钠通道电流,细胞内微电极技术记录心室乳头肌的动作电位和心电图机记录豚鼠的心电图。使用与心肌细胞钠通道有高度亲和力的海葵毒素(sea anemone toxin,ATXⅡ)改变钠通道开放的动力过程,从三个水平来研究钠通道、动作电位、心电图变化的关系,并试图探讨长QT综合征(long QT syndrome,LQTs)的发病机制。结果显示:ATXⅡ使钠通道的开放频率增加,钠通道中“长时间开放模式”的开放时间常数增大,动作电位的持续时间APD₅₀和APD₉₀也分别增加了23%和27%。ATXⅡ使动物心电图QT间期延长18.6%,QTc(校正的QT间期)增大18.9%。这些结果提示,钠通道动力过程的变化对动作电位和心电图QT间期有重要影响,钠通道功能或结构的变异可能是临床上部分长QT综合征产生的原因。
关键词：钠通道;ATXⅡ;动作电位;心电图;长QT综合征
分类号：Q463　文献标识码：A

Effect of ATXⅡ on opening modes of myocyte sodium channel, action potential and QT intervals of ECG

LI Ci-Zhen（Department of Physiology, Shanghai Second Medical University, Shanghai 200025）　
WANG Hong-Wei（Department of Physiology, Shanghai Second Medical University, Shanghai 200025）　
LIU Jian-Li（Department of Physiology, Shanghai Second Medical University, Shanghai 200025）　
LIU Kai（Department of Physiology, Shanghai Second Medical University, Shanghai 200025）　
YANG Zhi-Fang（Department of Physiology, Shanghai Second Medical University, Shanghai 200025）　
LIU Yuan-Mou（Department of Physiology, Shanghai Second Medical University, Shanghai 200025）　

Abstract：Single sodium channel currents were recorded by patch clamp technique in isolated guinea-pig ventricular myocytes, and action potentials of papillary muscle and ECG were conventionally measured. Sea anemone toxin (ATXⅡ), a high affinity toxin to sodium channel, was used to change the sodium channel dynamics. Changes in the duration of action potentials and the QT interval of ECG depending on the channel modes were studied in order to provide hints to an understanding of pathogenesis of the long QT syndrome (a genetic disease). With the binding of ATXⅡ to the sodium channel, the occurrence frequency and the open time constant of the “long opening” mode of single Na channels increased significantly, whereas the action potential durations, APD₅₀ and APD₉₀, were prolonged by 23% and 27% respectively. Following application of ATXⅡ, on the other hand, the QT interval and the QTc, a rectified QT interval, increased by 18. 6% and 18. 9% respectively. The results suggest that the dynamics or modes of Na channel play an important role in determining the action potential duration and the QT interval of ECG. The dynamical changes in Na channels induced by genetic mutation may be partially responsible for the long QT syndrome.
Keywords：sodium channel; ATXⅡ; action potential; ECG; long QT syndrome

基金项目：This work was supported by the National Natural Science Foundation of China (No.39770279, 39870770) and Shanghai Education-Development Foundation (No.99B02)
作者单位：李慈珍（上海第二医科大学生理教研室, 上海 200025）　
　　　　　王红卫（上海第二医科大学生理教研室, 上海 200025）　
　　　　　刘建立（上海第二医科大学生理教研室, 上海 200025）　
　　　　　刘凯（上海第二医科大学生理教研室, 上海 200025）　
　　　　　杨智日方（上海第二医科大学生理教研室, 上海 200025）　
　　　　　刘远谋（上海第二医科大学生理教研室, 上海 200025）　

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收稿日期：2000年7月10日

修稿日期：2000年10月26日