Knock-Out of the Potassium Channel TASK-1 Leads to a Prolonged QT Interval and a Disturbed QRS Complex

被引：70

作者：

Decher, Niels ^{[1
]}

Wemhoener, Konstantin ^{[1
]}

Rinne, Susanne ^{[1
]}

Netter, Michael F. ^{[1
]}

Zuzarte, Marylou ^{[1
]}

Aller, Maria I.

Kaufmann, Susann G. ^{[2
]}

Li, Xian Tao ^{[1
]}

Meuth, Sven G. ^{[3
,4
]}

Daut, Juergen ^{[1
]}

Sachse, Frank B. ^{[5
,6
]}

Maier, Sebastian K. G. ^{[2
]}

机构：

[1] Univ Marburg, Inst Physiol, D-35037 Marburg, Germany

[2] Med Klin & Poliklin 1, Wurzburg, Germany

[3] Univ Munster, Inst Physiol Neuropathophysiol, Munster, Germany

[4] Univ Munster, Klin & Poliklin Neurol Entzundliche Erkrankungen, Munster, Germany

[5] Univ Utah, Nora Eccles Harrison Cardiovasc Res & Training In, Salt Lake City, UT USA

[6] Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2011年 / 28卷 / 01期

关键词：

Prolonged QT interval; TASK-1; knock-out; Cardiac repolarization; In vivo electrophysiology; Ventricular arrhythmias; BACKGROUND K+ CHANNEL; CARDIAC REPOLARIZATION; MICE; HEART; EXPRESSION; ANESTHETICS; PACEMAKER; SUBUNITS;

D O I：

10.1159/000331715

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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

引用

页码：77 / 86

页数：10

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