Distinctive electrophysiological characteristics of right ventricular out-flow tract cardiomyocytes

Authors

  • Yen-Yu Lu,

    1. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
    2. Division of Cardiology, Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei City, Taiwan
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    • The first two authors (YY Lu and FP Chung) contributed equally to this study.
  • Fa-Po Chung,

    1. Division of Cardiology and Cardiovascular Research Center, Veterans General Hospital-Taipei, Taipei, Taiwan
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    • The first two authors (YY Lu and FP Chung) contributed equally to this study.
  • Yao-Chang Chen,

    1. Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan
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  • Chin-Feng Tsai,

    1. Division of Cardiology, Department of Internal Medicine, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung, Taiwan
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  • Yu-Hsun Kao,

    1. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
    2. Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
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  • Tze-Fan Chao,

    1. Division of Cardiology and Cardiovascular Research Center, Veterans General Hospital-Taipei, Taipei, Taiwan
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  • Jen-Hung Huang,

    1. Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
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  • Shih-Ann Chen,

    1. Division of Cardiology and Cardiovascular Research Center, Veterans General Hospital-Taipei, Taipei, Taiwan
    2. School of Medicine, National Yang-Ming University, Taipei, Taiwan
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  • Yi-Jen Chen

    Corresponding author
    1. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
    2. Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
    • Correspondence to: Yi-Jen CHEN,

      Division of Cardiovascular Medicine,

      Wan Fang Hospital, Taipei Medical University,

      No. 111, Sec. 3, Hsing-Long Rd,

      Taipei 116, Taiwan.

      Tel.: +886-2-28757156

      Fax: +886-2-29339378; +886-2-28735656

      E-mail: a9900112@ms15.hinet.net

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Abstract

Ventricular arrhythmias commonly originate from the right ventricular out-flow tract (RVOT). However, the electrophysiological characteristics and Ca2+ homoeostasis of RVOT cardiomyocytes remain unclear. Whole-cell patch clamp and indo-1 fluorometric ratio techniques were used to investigate action potentials, Ca2+ 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 Ca2+/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 Ca2+ transients, higher Ca2+ stores, higher late Na+ and transient outward K+ currents, but smaller delayed rectifier K+, L-type Ca2+ currents and Na+-Ca2+ 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 Ca2+ content, which could contribute to the high RVOT arrhythmogenic activity.

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