Cellular basis for electrocardiographic and arrhythmic manifestations of Andersen-Tawil syndrome (LQT7)
Cellular basis for electrocardiographic and arrhythmic manifestations of Andersen-Tawil syndrome (LQT7)
复制标题
DOI：
10.1016/j.hrthm.2005.11.026
复制
发表时间：
2006-03-01
期刊：
影响因子：
5.5
通讯作者：
Antzelevitch, C
中科院分区：
文献类型：
--
作者：
Tsuboi, M;Antzelevitch, C
背景 Andersen-Tawil 综合征是一种与心电图周期性麻痹和长 QT 间期相关的骨骼肌综合征，与 KCNJ2 缺陷有关，KCNJ2 是编码内向整流钾通道 (I-KI) 的基因。 目的 本研究的目的是检查 Andersen-Tawil 综合征心电图和心律失常表现背后的细胞机制。 方法 研究 KCNJ2 功能丧失突变的影响对于造成 Andersen-Tawil 综合征的原因，我们在动脉灌注楔形制剂中使用氯化钡 (BaCl2) 来抑制 I-KI。同时记录心内膜、心中膜和心外膜细胞的跨膜动作电位 (AP) 以及跨壁心电图。结果 BaCl2（1 至 30 μM）产生浓度依赖性 QT 间期延长，继发于三种细胞类型的 AP 持续时间均匀延长。 QT 间期延长，但跨壁复极离散度 (TDR) 不增加。低细胞外钾 (2.0 mM)、异丙肾上腺素 (20-50 nM) 和在 10 μM BaCl2 存在下温度突然升高 (36°C-39°C) 不会显着增加 TDR，但会增加异位期外收缩活动。在任何条件下均未观察到早期后除极。从未观察到自发性尖端扭转型室速心律失常，也无法在任何研究条件下通过程序化电刺激诱发自发性尖端扭转型室速。 结论 我们的研究结果让我们了解了为什么与 Andersen-Tawil 综合征相关的 QT 延长在临床上相对良性，并为 TDR 的增加而不是 QT 间期的增加导致尖端扭转型室速的发生提供了进一步的支持。
BACKGROUND Andersen-Tawil syndrome, a skeletal muscle syndrome associated with periodic paralysis and long QT intervals on the ECG, has been linked to defects in KCNJ2, the gene encoding for the inward rectifier potassium channel (I-KI.)OBJECTIVES The purpose of this study was to examine the cellular mechanisms underlying the ECG and arrhythmic manifestations of Andersen-Tawil syndrome.METHODS To investigate the effects of KCNJ2 loss-of-function mutations responsible for Andersen-Tawil syndrome, we used barium chloride (BaCl2) to inhibit I-KI in arterially perfused wedge preparation. Transmembrane action potentials (APs) were simultaneously recorded from endocardial, midmyocardial, and epicardial cells, together with a transmural ECG.RESULTS BaCl2 (1 to 30 mu M) produced a concentration-dependent prolongation of the QT interval, secondary to a homogeneous prolongation of AP duration of the three cell types. QT interval was prolonged without an increase in transmural dispersion of repolarization (TDR). Low extracellular potassium (2.0 mM), isoproterenol (20-50 nM), and an abrupt increase in temperature (36 degrees C-39 degrees C) in the presence of 10 mu M BaCl2 did not significantly increase TDR but increased ectopic extrasystolic activity. Early afterdepolarizations were not observed under any condition. Spontaneous torsades de pointes arrhythmias were never observed, nor could they be induced with programmed electrical stimulation under any of the conditions studied.CONCLUSION Our results provide an understanding of why QT prolongation associated with Andersen-Tawil syndrome is relatively benign in the clinic and provide further support for the hypothesis that the increase in TDR, rather than QT interval, is responsible for development of torsades de pointes.