title: Cloning, functional characterization, and remodeling of K2P3.1 (TASK-1) potassium channels in a porcine model of atrial fibrillation and heart failure.
abstract: BACKGROUND
  Effective treatment of atrial fibrillation (AF) remains an unmet need. Human K2P3.1 (TASK-1) K(+) channels display atrial-specific expression and may serve as novel antiarrhythmic targets. In rodents, inhibition of K2P3.1 causes prolongation of action potentials and QT intervals. We used a porcine model to further elucidate the significance of K2P3.1 in large mammals.
  
  
  OBJECTIVE
  The purpose of this study was to study porcine (p)K2P3.1 channel function and cardiac expression and to analyze pK2P3.1 remodeling in AF and heart failure (HF).
  
  
  METHODS
  The porcine K2P3.1 ortholog was amplified and characterized using voltage-clamp electrophysiology. K2P3.1 mRNA expression and remodeling were studied in domestic pigs during AF and HF induced by atrial burst pacing.
  
  
  RESULTS
  Porcine K2P3.1 cDNA encodes a channel protein with 97% identity to human K2P3.1. K(+) currents recorded from Xenopus oocytes expressing pK2P3.1 were functionally and pharmacologically similar to their human counterparts. In the pig, K2P3.1 mRNA was predominantly expressed in atrial tissue. AF and HF were associated with reduction of K2P3.1 mRNA levels by 85.1% (right atrium) and 77.0% (left atrium) at 21-day follow-up. In contrast, ventricular K2P3.1 expression was low and not significantly affected by AF/HF.
  
  
  CONCLUSIONS
  Porcine K2P3.1 channels exhibit atrial expression and functional properties similar to their human orthologs, supporting a general role as antiarrhythmic drug targets. K2P3.1 down-regulation in AF with HF may indicate functional relevance of the channel that remains to be validated in prospective interventional studies.
authors: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors: Constanze
authors: C
authors: Schmidt
authors: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors: Felix
authors: F
authors: Wiedmann
authors: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors: Clara
authors: C
authors: Langer
authors: Institute of Nanotechnology, Karlsruhe Institute of Technology, Karlsruhe, Germany.
authors: Frank
authors: F
authors: Tristram
authors: Institute of Nanotechnology, Karlsruhe Institute of Technology, Karlsruhe, Germany.
authors: Priya
authors: P
authors: Anand
authors: Institute of Nanotechnology, Karlsruhe Institute of Technology, Karlsruhe, Germany.
authors: Wolfgang
authors: W
authors: Wenzel
authors: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors: Patrick
authors: P
authors: Lugenbiel
authors: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors: Patrick A
authors: PA
authors: Schweizer
authors: Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
authors: Hugo A
authors: HA
authors: Katus
authors: Department of Cardiology, University of Heidelberg, Heidelberg, Germany. Electronic address: dierk.thomas@med.uni-heidelberg.de.
authors: Dierk
authors: D
authors: Thomas
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D018408:Patch-Clamp Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D013552:Swine
chemical_list: D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D012333:RNA, Messenger; C420132:potassium channel subfamily K member 3
keywords: Atrial fibrillation; Background potassium current; Cardiac action potential; Electrical remodeling; K(2P) channel