title: Changes in microRNA-1 expression and IK1 up-regulation in human atrial fibrillation.
abstract: BACKGROUND
  Atrial fibrillation (AF) is associated with increased inward-rectifier current activity that may stabilize atrial rotors maintaining the arrhythmia. Left atrial (LA) structures are important for AF maintenance, but previous studies have mostly evaluated changes in the right atrium. MicroRNA-1 (miR-1) reciprocally regulates inwardly rectifying potassium channel (Kir)2.1 expression in coronary disease, contributing to arrhythmogenesis.
  
  
  OBJECTIVE
  This study sought to evaluate changes in miR-1 and Kir2 subunit expression in relation to I(K1) alterations in LA of patients with persistent AF.
  
  
  METHODS
  Atrial tissue was obtained from 62 patients (31 with AF) undergoing mitral valve repair or bypass grafting. Currents were recorded from isolated cells. Proteins were quantified from immunoblots. mRNA and miR-1 levels were measured with real-time polymerase chain reaction. Immunohistochemistry was applied to localize connexin (Cx) 43.
  
  
  RESULTS
  I(K1) density was increased in LA cells from patients with AF (at -100 mV: -5.9 +/- 1.3 vs. -2.7 +/- 0.7 sinus rhythm, P <.05). There was a corresponding increase in Kir2.1 protein expression, but no change in other Kir or Cx proteins. Expression of inhibitory miR-1 was reduced by approximately 86% in tissue samples of AF patients. Kir2.1 mRNA was significantly increased. No change in Cx43 localization occurred. Ex vivo tachystimulation of human atrial slices up-regulated Kir2.1 and down-regulated miR-1, suggesting a primary role of atrial rate in miR-1 down-regulation and I(K1) up-regulation.
  
  
  CONCLUSIONS
  miR-1 levels are greatly reduced in human AF, possibly contributing to up-regulation of Kir2.1 subunits, leading to increased I(K1). Because up-regulation of inward-rectifier currents is important for AF maintenance, these results provide potential new insights into molecular mechanisms of AF with potential therapeutic implications.
authors: Division of Cardiology, Goethe-University, Frankfurt, Germany.
authors: Zenawit
authors: Z
authors: Girmatsion
authors: Peter
authors: P
authors: Biliczki
authors: Angelika
authors: A
authors: Bonauer
authors: Gerhard
authors: G
authors: Wimmer-Greinecker
authors: Mirella
authors: M
authors: Scherer
authors: Anton
authors: A
authors: Moritz
authors: Alicia
authors: A
authors: Bukowska
authors: Andreas
authors: A
authors: Goette
authors: Stanley
authors: S
authors: Nattel
authors: Stefan H
authors: SH
authors: Hohnloser
authors: Joachim R
authors: JR
authors: Ehrlich
mesh_terms: D000200:Action Potentials; D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism; D004594:Electrophysiology; D005260:Female; D006325:Heart Atria / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D017630:Connexins; D035683:MicroRNAs; D024661:Potassium Channels, Inwardly Rectifying