title: The role of gap junctions in stretch-induced atrial fibrillation.
abstract: OBJECTIVE
  The aim of this study was to investigate the role of gap junctions in atrial fibrillation (AF) by analysing the effects of a gap junction enhancer and blocker on AF vulnerability and electrophysiological properties of isolated hearts.
  
  
  RESULTS
  The acute atrial stretch model of AF in the isolated rabbit heart was used. Sustained AF (SAF) was induced by a burst of high-frequency stimulation of the Bachmann's bundle. The effective refractory period (ERP) was measured, and the total conduction time (TCT) and the pattern of conduction of the anterior surface of the left atrium were monitored by using an optical mapping system. The effect of enhancing gap junction function by 100-1000 nM rotigaptide (ZP123) and block by 30 μM carbenoxolone on these parameters was measured. SAF inducibility was increased with an elevation of intra-atrial pressure. Enhanced gap junction conductance induced by treatment with 100-1000 nM rotigaptide reduced SAF inducibility, and the gap junction blocker carbenoxolone increased SAF inducibility. In the absence of gap junction enhancer or blocker, normal conduction was observed at 0 cmH2O. When intra-atrial pressure was raised to 12 cmH2O, the conduction pattern was changed to a heterogeneous zig-zag pattern and TCT was prolonged. Conduction pattern was not affected by either agent. Rotigaptide shortened TCT, whereas carbenoxolone prolonged TCT. ERP was significantly shortened with an increase in intra-atrial pressure, but ERP was unaffected by either agent.
  
  
  CONCLUSIONS
  Gap junction modulators changed AF inducibility through their effects on atrial conduction, not by altering ERP.
authors.affiliation: Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan nueda@riem.nagoya-u.ac.jp.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Ueda
authors.affiliation: Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Honjo
authors.affiliation: Nagoya University, Nagoya, Japan.
authors.forename: Itsuo
authors.initials: I
authors.lastname: Kodama
authors.affiliation: Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Kaichiro
authors.initials: K
authors.lastname: Kamiya
mesh_terms: D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D062185:Atrial Pressure; D002229:Carbenoxolone / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D000067268:Isolated Heart Preparation; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D009470:Muscle Spindles / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009842:Oligopeptides / Q000494:pharmacology; D011817:Rabbits; D012032:Refractory Period, Electrophysiological; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D009842:Oligopeptides; C477643:rotigaptide; D002229:Carbenoxolone
keywords: Atrial fibrillation; Carbenoxolone; Gap junction; Rotigaptide