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目的探讨长QT综合征3型(LQT3)的致病基因SCN5A及其相关的变异产生室性心律失常的细胞电生理机制。方法从野生型小鼠和SCN5A+/△的小鼠心脏中分离心室肌细胞,采用电流嵌和全细胞膜片钳技术分析了携带SCN5A△KPQ变异的小鼠心肌细胞的电生理学表型。结果与野生型细胞[(55.0±6.6)ms,n=7]相比,SCN5A+/△心肌细胞[(152±17.8)ms,n=6]动作电位明显延长(P<0.01);在SCN5A+/△心肌细胞中观察到早期后除极,而野生型心肌细胞中则未出现;全细胞记录表明SCN5A+/△心肌细胞有晚期持续钠电流,而在野生型细胞中未见。结论晚期持续钠电流可能是与SCN5A△KPQ突变相关的室性心律失常的主要机制。
Objective To investigate the electrophysiological mechanism of ventricular arrhythmia induced by SCN5A and its related mutations in long QT syndrome type 3 (LQT3). Methods Ventricular myocytes were isolated from wild-type mice and SCN5A + / △ mouse hearts, and the electrophysiological phenotypes of mouse cardiomyocytes carrying SCN5A △ KPQ mutation were analyzed by current-embedded whole-cell patch clamp technique. Results The action potentials of SCN5A + / △ myocytes [(152 ± 17.8) ms, n = 6] were significantly longer than those of wild type cells [(55.0 ± 6.6) ms, n = 7] △ Depolarization was observed early in cardiomyocytes but not in wild-type cardiomyocytes. Whole-cell recordings showed that SCN5A + / △ cardiomyocytes had late persistent sodium currents but not in wild-type cells. Conclusions Continuous sodium current in late stage may be the main mechanism of ventricular arrhythmia associated with SCN5A △ KPQ mutation.