Distinctive electrophysiological characteristics of right ventricular out‐flow tract cardiomyocytes. Issue 8 (9th June 2014)

• Record Type: Journal Article
• Authors: Lu, Yen‐Yu; Chung, Fa‐Po; Chen, Yao‐Chang; Tsai, Chin‐Feng; Kao, Yu‐Hsun; Chao, Tze‐Fan; Huang, Jen‐Hung; Chen, Shih‐Ann; Chen, Yi‐Jen
• Is Part Of: Journal of cellular and molecular medicine. Volume 18:Issue 8(2014)
• Page Start: 1540
• Page End: 1548
• Publication Date: 2014-06-09
• Subjects: Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.12329
• Languages: English
• ISSNs: 1582-1838

Abstract

<abstract abstract-type="main" id="jcmm12329-abs-0001"> <title>Abstract</title> <p>Ventricular arrhythmias commonly originate from the right ventricular out‐flow tract (RVOT). However, the electrophysiological characteristics and Ca<sup>2+</sup> homoeostasis of RVOT cardiomyocytes remain unclear. Whole‐cell patch clamp and indo‐1 fluorometric ratio techniques were used to investigate action potentials, Ca<sup>2+</sup> 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<sup>2+</sup>/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<sup>+</sup>/K<sup>+</sup> 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<sup>2+</sup> transients, higher Ca<sup>2+</sup> stores, higher late Na<sup>+</sup> and transient outward K<sup>+</sup> currents, but smaller delayed rectifier K<sup>+</sup>, L‐type Ca<sup>2+</sup> currents and Na<sup>+</sup>‐Ca<sup>2+</sup> exchanger currents. RVOT cardiomyocytes showed significantly more pacing‐induced delayed afterdepolarizations (22% <italic>versus</italic> 0%, <italic>P</italic> < 0.05) and ouabain‐induced ventricular arrhythmias (94% <italic>versus</italic> 61%, <italic>P</italic> < 0.05) than RVA cardiomyocytes. Consistently, it took longer time (9 ± 1 <italic>versus</italic> 4 ± 1 min., <italic>P</italic> < 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<sup>2+</sup> content, which could contribute to the high RVOT arrhythmogenic activity.</p> </abstract>