title: Gap junction modifiers regulate electrical activities of the sinoatrial node and pulmonary vein: Therapeutic implications in atrial arrhythmogenesis.
abstract: BACKGROUND
  Gap junction (GJ) dysfunctions predispose cardiac tissues to various arrhythmias. Sinoatrial node (SAN) and pulmonary veins (PVs) are closely related atrial dysrhythmia. This study evaluated whether GJ modifications modulate SAN and PVs electrical activities.
  
  
  METHODS
  Conventional microelectrodes were used to record action potentials in isolated rabbit SAN, PVs, and connected PV-SAN tissue preparations before and after heptanol (GJ inhibitor) and PQ1 (GJ enhancer) administration with and without isoproterenol. A whole-cell patch clamp was used to record the electrical activities before and after heptanol in single SAN and PV cardiomyocytes.
  
  
  RESULTS
  Heptanol (1, 3, and 10μM) reduced the spontaneous beating rates of isolated SAN preparations but not PVs. Heptanol (10μM) decelerated the SAN leading rhythm in the PV-SAN preparations and induced PV burst firings without (3 of 6, 50%) and with (6 of 6, 100%) isoproterenol (1μM). Heptanol (10μM) also reduced the spontaneous beating rates in single SAN cardiomyocyte, but not PV cardiomyocyte, with a decreased pacemaker current. PQ1 (50 and 500nM) treatment did not change the spontaneous beating rates in isolated SAN and PV preparations. In the connected PV-SAN preparations, PQ1 (500nM) did not induce any PV firing even having additional isoproterenol treatment (1μM). Moreover, PQ1 (500nM) prevented heptanol-induced electrical changes in SAN and PVs preparations.
  
  
  CONCLUSIONS
  GJ dysfunction modulates SAN and PV electrical activity, which may contribute to atrial arrhythmogenesis. GJ enhancer has a therapeutic potential in SAN dysfunction and atrial arrhythmogenesis.
authors.affiliation: Division of Cardiology, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan.
authors.forename: Chien-Jung
authors.initials: CJ
authors.lastname: Chang
authors.affiliation: Division of Cardiology, Chi-Mei Medical Center, Tainan, Taiwan; Chung Shan Medical University, Department of Internal Medicine, Taichung, Taiwan.
authors.forename: Chen-Chuan
authors.initials: CC
authors.lastname: Cheng
authors.affiliation: Department of Biomedical Engineering and Institute of Physiology, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Hsun
authors.initials: YH
authors.lastname: Kao
authors.affiliation: National Yang-Ming University, School of Medicine, Taipei, Taiwan; Division of Cardiology and Cardiovascular Research Center, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: a9900112@ms15.hinet.net.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology / Q000517:prevention & control; D002317:Cardiovascular Agents / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D006325:Heart Atria / Q000503:physiopathology; D019850:Heptanol / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D011667:Pulmonary Veins / Q000503:physiopathology; D011817:Rabbits; D012849:Sinoatrial Node / Q000503:physiopathology
chemical_list: D000634:Aminoquinolines; D002317:Cardiovascular Agents; C577576:PQ1 compound; D019850:Heptanol; D007545:Isoproterenol
keywords: Atrial fibrillation; Gap junction; PQ1; Pacemaker current; Pulmonary vein; Sinoatrial node