title: Distinctive electrophysiological characteristics of right ventricular out-flow tract cardiomyocytes.
abstract: Ventricular arrhythmias commonly originate from the right ventricular out-flow tract (RVOT). However, the electrophysiological characteristics and Ca(2+) homoeostasis of RVOT cardiomyocytes remain unclear. Whole-cell patch clamp and indo-1 fluorometric ratio techniques were used to investigate action potentials, Ca(2+) homoeostasis and ionic currents in isolated cardiomyocytes from the rabbit RVOT and right ventricular apex (RVA). Conventional microelectrodes were used to record the electrical activity before and after (KN-93, a Ca(2+) /calmodulin-dependent kinase II inhibitor, or ranolazine, a late sodium current inhibitor) treatment in RVOT and RVA tissue preparations under electrical pacing and ouabain (Na(+) /K(+) ATPase inhibitor) administration. In contrast to RVA cardiomyocytes, RVOT cardiomyocytes were characterized by longer action potential duration measured at 90% and 50% repolarization, larger Ca(2+) transients, higher Ca(2+) stores, higher late Na(+) and transient outward K(+) currents, but smaller delayed rectifier K(+) , L-type Ca(2+) currents and Na(+) -Ca(2+) exchanger currents. RVOT cardiomyocytes showed significantly more pacing-induced delayed afterdepolarizations (22% versus 0%, P < 0.05) and ouabain-induced ventricular arrhythmias (94% versus 61%, P < 0.05) than RVA cardiomyocytes. Consistently, it took longer time (9 ± 1 versus 4 ± 1 min., P < 0.05) to eliminate ouabain-induced ventricular arrhythmias after application of KN-93 (but not ranolazine) in the RVOT in comparison with the RVA. These results indicate that RVOT cardiomyocytes have distinct electrophysiological characteristics with longer AP duration and greater Ca(2+) content, which could contribute to the high RVOT arrhythmogenic activity.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiology, Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei City, Taiwan.
authors.forename: Yen-Yu
authors.initials: YY
authors.lastname: Lu
authors.forename: Fa-Po
authors.initials: FP
authors.lastname: Chung
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Chin-Feng
authors.initials: CF
authors.lastname: Tsai
authors.forename: Yu-Hsun
authors.initials: YH
authors.lastname: Kao
authors.forename: Tze-Fan
authors.initials: TF
authors.lastname: Chao
authors.forename: Jen-Hung
authors.initials: JH
authors.lastname: Huang
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000473:pathology*; D001596:Benzylamines / Q000494:pharmacology; D053840:Brugada Syndrome; D002118:Calcium / Q000378:metabolism*; D000075224:Cardiac Conduction System Disease; D055724:Electrophysiological Phenomena; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006329:Heart Conduction System / Q000002:abnormalities* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011817:Rabbits; D000069458:Ranolazine; D019831:Sodium-Calcium Exchanger; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D000083:Acetanilides; D001596:Benzylamines; D002118:Calcium; D004791:Enzyme Inhibitors; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D000069458:Ranolazine; D019831:Sodium-Calcium Exchanger; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides
keywords: arrhythmogenicity; calcium handling; right ventricular out-flow tract; ventricular arrhythmias