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BACKGROUND/AIMS: Atrial fibrillation is the most common arrhythmia in the elderly, and potassium channels with atrium-specific expression have been discussed as targets to treat atrial fibrillation. Our aim was to characterize TASK-1 channels in human heart and to functionally describe the role of the atrial whole cell current I(TASK-1).
METHODS AND RESULTS: Using quantitative PCR, we show that TASK-1 is predominantly expressed in the atria, auricles and atrio-ventricular node of the human heart. Single channel recordings show the functional expression of TASK-1 in right human auricles. In addition, we describe for the first time the whole cell current carried by TASK-1 channels (I(TASK-1)) in human atrial tissue. We show that I(TASK-1) contributes to the sustained outward current I(Ksus) and that I(TASK-1) is a major component of the background conductance in human atrial cardiomyocytes. Using patch clamp recordings and mathematical modeling of action potentials, we demonstrate that modulation of I(TASK-1) can alter human atrial action potential duration.
CONCLUSION: Due to the lack of ventricular expression and the ability to alter human atrial action potential duration, TASK-1 might be a drug target for the treatment of atrial fibrillation.
Abbruzzese,
Modification of hERG1 channel gating by Cd2+.
2010, Pubmed,
Xenbase
Abbruzzese,
Modification of hERG1 channel gating by Cd2+.
2010,
Pubmed
,
Xenbase Barth,
Reprogramming of the human atrial transcriptome in permanent atrial fibrillation: expression of a ventricular-like genomic signature.
2005,
Pubmed Burashnikov,
New developments in atrial antiarrhythmic drug therapy.
2010,
Pubmed Bustamante,
Isolation of single atrial and ventricular cells from the human heart.
1982,
Pubmed Chandler,
Molecular architecture of the human sinus node: insights into the function of the cardiac pacemaker.
2009,
Pubmed Chugh,
Epidemiology and natural history of atrial fibrillation: clinical implications.
2001,
Pubmed Courtemanche,
Ionic mechanisms underlying human atrial action potential properties: insights from a mathematical model.
1998,
Pubmed Decher,
Structural basis for competition between drug binding and Kvbeta 1.3 accessory subunit-induced N-type inactivation of Kv1.5 channels.
2005,
Pubmed
,
Xenbase Decher,
Knock-out of the potassium channel TASK-1 leads to a prolonged QT interval and a disturbed QRS complex.
2011,
Pubmed Dixon,
Quantitative analysis of potassium channel mRNA expression in atrial and ventricular muscle of rats.
1994,
Pubmed Donner,
Functional role of TASK-1 in the heart: studies in TASK-1-deficient mice show prolonged cardiac repolarization and reduced heart rate variability.
2011,
Pubmed Duprat,
TASK, a human background K+ channel to sense external pH variations near physiological pH.
1997,
Pubmed
,
Xenbase Ehrlich,
Atrial-selective pharmacological therapy for atrial fibrillation: hype or hope?
2009,
Pubmed Fedida,
Identity of a novel delayed rectifier current from human heart with a cloned K+ channel current.
1993,
Pubmed Gaborit,
Human atrial ion channel and transporter subunit gene-expression remodeling associated with valvular heart disease and atrial fibrillation.
2005,
Pubmed Goldstein,
Potassium leak channels and the KCNK family of two-P-domain subunits.
2001,
Pubmed Graham,
Expression of a two-pore domain K+ channel (TASK-1) in developing avian and mouse ventricular conduction systems.
2006,
Pubmed Guo,
Roles of the voltage-gated K+ channel subunits, Kv 1.5 and Kv 1.4, in the developmental changes of K+ currents in cultured neonatal rat ventricular cells.
1997,
Pubmed Kim,
TBAK-1 and TASK-1, two-pore K(+) channel subunits: kinetic properties and expression in rat heart.
1999,
Pubmed Maier,
Stimulation of L-type Ca2+ current in human atrial myocytes by insulin.
1999,
Pubmed McBride,
The emerging role of antiarrhythmic compounds with atrial selectivity in the management of atrial fibrillation.
2009,
Pubmed Michael,
Remodelling of cardiac repolarization: how homeostatic responses can lead to arrhythmogenesis.
2009,
Pubmed Mitcheson,
A structural basis for drug-induced long QT syndrome.
2000,
Pubmed
,
Xenbase Musset,
Effects of divalent cations and spermine on the K+ channel TASK-3 and on the outward current in thalamic neurons.
2006,
Pubmed Nattel,
Arrhythmogenic ion-channel remodeling in the heart: heart failure, myocardial infarction, and atrial fibrillation.
2007,
Pubmed Nattel,
Ion-channel mRNA-expression profiling: Insights into cardiac remodeling and arrhythmic substrates.
2010,
Pubmed Nattel,
Innovative approaches to anti-arrhythmic drug therapy.
2006,
Pubmed Nerbonne,
Molecular basis of functional voltage-gated K+ channel diversity in the mammalian myocardium.
2000,
Pubmed Nerbonne,
Molecular physiology of cardiac repolarization.
2005,
Pubmed Putzke,
The acid-sensitive potassium channel TASK-1 in rat cardiac muscle.
2007,
Pubmed
,
Xenbase Snyders,
A rapidly activating and slowly inactivating potassium channel cloned from human heart. Functional analysis after stable mammalian cell culture expression.
1993,
Pubmed Streit,
A specific two-pore domain potassium channel blocker defines the structure of the TASK-1 open pore.
2011,
Pubmed
,
Xenbase Van Wagoner,
Outward K+ current densities and Kv1.5 expression are reduced in chronic human atrial fibrillation.
1997,
Pubmed Wang,
Sustained depolarization-induced outward current in human atrial myocytes. Evidence for a novel delayed rectifier K+ current similar to Kv1.5 cloned channel currents.
1993,
Pubmed Wettwer,
Role of IKur in controlling action potential shape and contractility in the human atrium: influence of chronic atrial fibrillation.
2004,
Pubmed Wilders,
Dynamic clamp: a powerful tool in cardiac electrophysiology.
2006,
Pubmed