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.
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.
Authors: Erich Wettwer; Ottó Hála; Torsten Christ; Jürgen F Heubach; Dobromir Dobrev; Michael Knaut; András Varró; Ursula Ravens Journal: Circulation Date: 2004-10-11 Impact factor: 29.690
Authors: Mark A Skarsfeldt; Thomas A Jepps; Sofia H Bomholtz; Lea Abildgaard; Ulrik S Sørensen; Emilie Gregers; Jesper H Svendsen; Jonas G Diness; Morten Grunnet; Nicole Schmitt; Søren-Peter Olesen; Bo H Bentzen Journal: Pflugers Arch Date: 2016-01-05 Impact factor: 3.657
Authors: Erin Harleton; Alessandra Besana; Parag Chandra; Peter Danilo; Tove S Rosen; Michael R Rosen; Michael Argenziano; Richard B Robinson; Steven J Feinmark Journal: Am J Physiol Heart Circ Physiol Date: 2014-11-26 Impact factor: 4.733
Authors: Erin Harleton; Alessandra Besana; George M Comas; Peter Danilo; Tove S Rosen; Michael Argenziano; Michael R Rosen; Richard B Robinson; Steven J Feinmark Journal: J Biol Chem Date: 2012-12-10 Impact factor: 5.157
Authors: Connor J Telles; Sarah E Decker; William W Motley; Alexander W Peters; Ali Poyan Mehr; Raymond A Frizzell; John N Forrest Journal: Am J Physiol Cell Physiol Date: 2016-09-21 Impact factor: 4.249