Knock-Out of the Potassium Channel TASK-1 Leads to a Prolonged QT Interval and a Disturbed QRS Complex
Knock-Out of the Potassium Channel TASK-1 Leads to a Prolonged QT Interval and a Disturbed QRS Complex
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DOI：
10.1159/000331715
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发表时间：
2011-01-01
影响因子：
--
通讯作者：
Maier, Sebastian K. G.
中科院分区：
文献类型：
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作者：
Decher, Niels;Wemhoener, Konstantin;Maier, Sebastian K. G.
背景/目标：本研究的目的是表征小鼠心室心肌细胞（I（ASK-1））中双孔结构域钾通道ASK-1（K2P3）的全细胞电流，并分析ASK-1（-/-）小鼠的心脏表型。方法和结果：我们使用阻断剂A293和Task-I（-/-）小鼠定量了心室I（Task-I）电流。Task-I（-/-）小鼠的体表心电图记录显示QTc间期延长和QRS波群增宽。在动物的交感神经刺激过程中，野生型小鼠和Task-I（-/-）小鼠之间的心电图差异消失。定量RT-PCR，膜片钳记录和血液动力学性能的测量的任务-1（-/-）小鼠显示没有重大的代偿性变化的离子通道转录。ASK-1（-/-）小鼠心肌细胞的动作电位记录表明，I（ASK-1）调节动作电位时程。我们的体内电生理研究表明，异氟烷，它激活了ASK-1，减慢野生型小鼠的心率和房室传导，但不是ASK-1（-/-）小鼠。总结：侵入性电生理导管方案的结果与在表面心电图中观察到的QRS时间延长相结合，指向心脏传导系统中的ASK-1的调节作用。版权所有（C）2011 S. Karger AG，巴塞尔
Background/Aims: The aim of the study was to characterize the whole cell current of the two-pore domain potassium channel TASK-1 (K2P3) in mouse ventricular cardiomyocytes (I(TASK-1)) and to analyze the cardiac phenotype of the TASK-1(-/-) mice. Methods and Results: We have quantified the ventricular I(TASK-1) current using the blocker A293 and TASK-1(-/-) mice. Surface electrocardiogram recordings of TASK-1(-/-) mice showed a prolonged QTc interval and a broadened QRS complex. The differences in electrocardiograms between wild type and TASK-1(-/-) mice disappeared during sympathetic stimulation of the animals. Quantitative RT-PCR, patch clamp recordings and measurements of hemodynamic performance of TASK-1(-/-) mice revealed no major compensatory changes in ion channel transcription. Action potential recordings of TASK-1(-/-) mouse cardiomyocytes indicated that I(TASK-1) modulates action potential duration. Our in vivo electrophysiological studies showed that isoflurane, which activates TASK-1, slowed heart rate and atrioventricular conduction of wild-type but not of TASK-1(-/-) mice. Conclusion: The results of an invasive electrophysiological catheter protocol in combination with the observed QRS time prolongation in the surface electrocardiogram point towards a regulatory role of TASK-1 in the cardiac conduction system. Copyright (C) 2011 S. Karger AG, Basel