Effects of a Na+/Ca2+ exchanger inhibitor on pulmonary vein electrical activity and ouabain-induced arrhythmogenicity

Wanwarang Wongcharoen, Yao Chang Chen, Yi Jen Chen, Che Ming Chang, Hung I. Yeh, Cheng I. Lin, Shih Ann Chen

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Objective: Pulmonary veins (PVs) are the most important focus for generation of atrial fibrillation. The Na+/Ca2+ exchange (NCX) current is important in PV electrical activity and cardiac glycosides-induced arrhythmias. The purpose of this study was to investigate whether KB-R7943, a NCX current blocker with preferential inhibition of the Ca2+ influx, may alter PV electrophysiological characteristics and reduce glycoside-induced arrhythmogenicity. Methods: Conventional microelectrodes were used to record the effects of KB-R7943 on action potentials and contractility in isolated rabbit PV tissue specimens with and without administration of ouabain. The ionic currents and intracellular calcium were studied in isolated single cardiomyocytes before and after KB-R7943 by the whole-cell patch clamp and indo-1 fluorimetric ratio techniques. Results: KB-R7943 (0, 3, 10, 30 μM) concentration-dependently prolonged APD50 and APD90 and decreased the PV firing rates (2.3 ± 1.2 Hz, 2.1 ± 1.2 Hz, 1.9 ± 0.9 Hz, 1.7 ± 1.1 Hz, n = 7, p <0.05) and incidences of delayed afterdepolarizations (DADs). KB-R7943 (3, 30 μM) decreased transient inward currents, Ca2+ transient and sarcoplasmic reticulum Ca2+ content. Ouabain (0, 0.1, 1 μM) concentration-dependently increased the PV firing rates and DADs in PVs with spontaneous activity (n = 7) and induced nonsustained spontaneous activity (1 μM) in the PVs without spontaneous activity (n = 14). However, in the presence of KB-R7943 (30 μM), ouabain (1 μM) did not increase the PV firing rates or induce spontaneous activity in the PVs without spontaneous activity (n = 7). Conclusions: KB-R7943 reduces the PV arrhythmogenic activity and prevents the ouabain-induced arrhythmogenicity. Our findings support the role of the NCX current in the PV electrical activity.

Original languageEnglish
Pages (from-to)497-508
Number of pages12
JournalCardiovascular Research
Volume70
Issue number3
DOIs
Publication statusPublished - Jun 1 2006

Fingerprint

Pulmonary Veins
Ouabain
Cardiac Glycosides
Sarcoplasmic Reticulum
Microelectrodes
Glycosides
2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate
Cardiac Myocytes
Atrial Fibrillation
Action Potentials
Cardiac Arrhythmias

Keywords

  • Atrial fibrillation
  • Glycosides
  • Na/Ca exchange current
  • Pulmonary vein
  • Triggered activity

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Effects of a Na+/Ca2+ exchanger inhibitor on pulmonary vein electrical activity and ouabain-induced arrhythmogenicity. / Wongcharoen, Wanwarang; Chen, Yao Chang; Chen, Yi Jen; Chang, Che Ming; Yeh, Hung I.; Lin, Cheng I.; Chen, Shih Ann.

In: Cardiovascular Research, Vol. 70, No. 3, 01.06.2006, p. 497-508.

Research output: Contribution to journalArticle

Wongcharoen, Wanwarang ; Chen, Yao Chang ; Chen, Yi Jen ; Chang, Che Ming ; Yeh, Hung I. ; Lin, Cheng I. ; Chen, Shih Ann. / Effects of a Na+/Ca2+ exchanger inhibitor on pulmonary vein electrical activity and ouabain-induced arrhythmogenicity. In: Cardiovascular Research. 2006 ; Vol. 70, No. 3. pp. 497-508.
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AU - Wongcharoen, Wanwarang

AU - Chen, Yao Chang

AU - Chen, Yi Jen

AU - Chang, Che Ming

AU - Yeh, Hung I.

AU - Lin, Cheng I.

AU - Chen, Shih Ann

PY - 2006/6/1

Y1 - 2006/6/1

N2 - Objective: Pulmonary veins (PVs) are the most important focus for generation of atrial fibrillation. The Na+/Ca2+ exchange (NCX) current is important in PV electrical activity and cardiac glycosides-induced arrhythmias. The purpose of this study was to investigate whether KB-R7943, a NCX current blocker with preferential inhibition of the Ca2+ influx, may alter PV electrophysiological characteristics and reduce glycoside-induced arrhythmogenicity. Methods: Conventional microelectrodes were used to record the effects of KB-R7943 on action potentials and contractility in isolated rabbit PV tissue specimens with and without administration of ouabain. The ionic currents and intracellular calcium were studied in isolated single cardiomyocytes before and after KB-R7943 by the whole-cell patch clamp and indo-1 fluorimetric ratio techniques. Results: KB-R7943 (0, 3, 10, 30 μM) concentration-dependently prolonged APD50 and APD90 and decreased the PV firing rates (2.3 ± 1.2 Hz, 2.1 ± 1.2 Hz, 1.9 ± 0.9 Hz, 1.7 ± 1.1 Hz, n = 7, p <0.05) and incidences of delayed afterdepolarizations (DADs). KB-R7943 (3, 30 μM) decreased transient inward currents, Ca2+ transient and sarcoplasmic reticulum Ca2+ content. Ouabain (0, 0.1, 1 μM) concentration-dependently increased the PV firing rates and DADs in PVs with spontaneous activity (n = 7) and induced nonsustained spontaneous activity (1 μM) in the PVs without spontaneous activity (n = 14). However, in the presence of KB-R7943 (30 μM), ouabain (1 μM) did not increase the PV firing rates or induce spontaneous activity in the PVs without spontaneous activity (n = 7). Conclusions: KB-R7943 reduces the PV arrhythmogenic activity and prevents the ouabain-induced arrhythmogenicity. Our findings support the role of the NCX current in the PV electrical activity.

AB - Objective: Pulmonary veins (PVs) are the most important focus for generation of atrial fibrillation. The Na+/Ca2+ exchange (NCX) current is important in PV electrical activity and cardiac glycosides-induced arrhythmias. The purpose of this study was to investigate whether KB-R7943, a NCX current blocker with preferential inhibition of the Ca2+ influx, may alter PV electrophysiological characteristics and reduce glycoside-induced arrhythmogenicity. Methods: Conventional microelectrodes were used to record the effects of KB-R7943 on action potentials and contractility in isolated rabbit PV tissue specimens with and without administration of ouabain. The ionic currents and intracellular calcium were studied in isolated single cardiomyocytes before and after KB-R7943 by the whole-cell patch clamp and indo-1 fluorimetric ratio techniques. Results: KB-R7943 (0, 3, 10, 30 μM) concentration-dependently prolonged APD50 and APD90 and decreased the PV firing rates (2.3 ± 1.2 Hz, 2.1 ± 1.2 Hz, 1.9 ± 0.9 Hz, 1.7 ± 1.1 Hz, n = 7, p <0.05) and incidences of delayed afterdepolarizations (DADs). KB-R7943 (3, 30 μM) decreased transient inward currents, Ca2+ transient and sarcoplasmic reticulum Ca2+ content. Ouabain (0, 0.1, 1 μM) concentration-dependently increased the PV firing rates and DADs in PVs with spontaneous activity (n = 7) and induced nonsustained spontaneous activity (1 μM) in the PVs without spontaneous activity (n = 14). However, in the presence of KB-R7943 (30 μM), ouabain (1 μM) did not increase the PV firing rates or induce spontaneous activity in the PVs without spontaneous activity (n = 7). Conclusions: KB-R7943 reduces the PV arrhythmogenic activity and prevents the ouabain-induced arrhythmogenicity. Our findings support the role of the NCX current in the PV electrical activity.

KW - Atrial fibrillation

KW - Glycosides

KW - Na/Ca exchange current

KW - Pulmonary vein

KW - Triggered activity

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