Distinctive electrophysiological characteristics of right ventricular out-flow tract cardiomyocytes

Yen Yu Lu, Fa Po Chung, Yao Chang Chen, Chin Feng Tsai, Yu Hsun Kao, Tze Fan Chao, Jen Hung Huang, Shih Ann Chen, Yi Jen Chen

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1540-1548
Number of pages9
JournalJournal of Cellular and Molecular Medicine
Volume18
Issue number8
DOIs
Publication statusPublished - 2014

Fingerprint

Cardiac Myocytes
Ouabain
Cardiac Arrhythmias
Action Potentials
Homeostasis
Calcium-Calmodulin-Dependent Protein Kinases
Microelectrodes
Sodium
Rabbits

Keywords

  • Arrhythmogenicity
  • Calcium handling
  • Right ventricular out-flow tract
  • Ventricular arrhythmias

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

Distinctive electrophysiological characteristics of right ventricular out-flow tract cardiomyocytes. / 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.

In: Journal of Cellular and Molecular Medicine, Vol. 18, No. 8, 2014, p. 1540-1548.

Research output: Contribution to journalArticle

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. / Distinctive electrophysiological characteristics of right ventricular out-flow tract cardiomyocytes. In: Journal of Cellular and Molecular Medicine. 2014 ; Vol. 18, No. 8. pp. 1540-1548.
@article{9a10dfa60e5d4b2bad238b5333aebd37,
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 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.",
keywords = "Arrhythmogenicity, Calcium handling, Right ventricular out-flow tract, Ventricular arrhythmias",
author = "Lu, {Yen Yu} and Chung, {Fa Po} and Chen, {Yao Chang} and Tsai, {Chin Feng} and Kao, {Yu Hsun} and Chao, {Tze Fan} and Huang, {Jen Hung} and Chen, {Shih Ann} and Chen, {Yi Jen}",
year = "2014",
doi = "10.1111/jcmm.12329",
language = "English",
volume = "18",
pages = "1540--1548",
journal = "Journal of Cellular and Molecular Medicine",
issn = "1582-1838",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Distinctive electrophysiological characteristics of right ventricular out-flow tract cardiomyocytes

AU - Lu, Yen Yu

AU - Chung, Fa Po

AU - Chen, Yao Chang

AU - Tsai, Chin Feng

AU - Kao, Yu Hsun

AU - Chao, Tze Fan

AU - Huang, Jen Hung

AU - Chen, Shih Ann

AU - Chen, Yi Jen

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Arrhythmogenicity

KW - Calcium handling

KW - Right ventricular out-flow tract

KW - Ventricular arrhythmias

UR - http://www.scopus.com/inward/record.url?scp=84912527868&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84912527868&partnerID=8YFLogxK

U2 - 10.1111/jcmm.12329

DO - 10.1111/jcmm.12329

M3 - Article

VL - 18

SP - 1540

EP - 1548

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

SN - 1582-1838

IS - 8

ER -