Effects of Ivabradine on the Pulmonary Vein Electrical Activity and Modulation of Pacemaker Currents and Calcium Homeostasis

Kazuyoshi Suenari; Yukiko Nakano; Yasuki Kihara; Kazuyoshi Suenari; Yao Chang Chen; Yi Jen Chen; Shih Ann Chen

doi:10.4020/jhrs.27.OP23_2

Effects of Ivabradine on the Pulmonary Vein Electrical Activity and Modulation of Pacemaker Currents and Calcium Homeostasis

Kazuyoshi Suenari, Yukiko Nakano, Yasuki Kihara, Kazuyoshi Suenari, Yao Chang Chen, Yi Jen Chen, Shih Ann Chen

Research output: Contribution to journal › Article › peer-review

Abstract

Introduction: Ivabradine is a novel heart rate decreasing agent with selective and specific antagonist effects on the pacemaker current (If). The aim of this study was to investigate the pharmacological effects of ivabradine on the pulmonary vein (PV) cardiomyocytes. Methods: Whole-cell patch clamp techniques and the indo-1 fluorimetric ratio technique were used to investigate the characteristics of the If and intracellular calcium (Ca²⁺i) in single isolated rabbit PV cardiomyocytes with pacemaker activity before and after an ivabradine administration (0.3, 3, 10, and 30 μM). Results: Ivabradine concentration-dependently decreased the spontaneous activity and the If in PV cardiomyocytes. The decreased extent of the PV beating rate or If by the different concentrations of ivabradine correlated well with the baseline PV beating rates. The IC50 of the spontaneous activity and If induced by ivabradine were 9.5μM and 3.5μM, respectively. Moreover, ivabradine (30uM, but not 3uM) decreased the Ca²+i transient in the PV cardiomyocytes and ivabradine (30 uM) decreased the L-type calcium current in the PV cardiomyocytes. Conclusion: Ivabradine decreased the pacemaker currents and Ca²+i transient in the PV cardiomyocytes, which may contribute to its inhibitory effects on the PV spontaneous activity.

Original language	English
Pages (from-to)	263
Number of pages	1
Journal	Journal of Arrhythmia
Volume	27
Issue number	4
DOIs	https://doi.org/10.4020/jhrs.27.OP23_2
Publication status	Published - 2011

Keywords

atrial fibrillation
pacemaker current
pulmonary vein

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.4020/jhrs.27.OP23_2

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title = "Effects of Ivabradine on the Pulmonary Vein Electrical Activity and Modulation of Pacemaker Currents and Calcium Homeostasis",

abstract = "Introduction: Ivabradine is a novel heart rate decreasing agent with selective and specific antagonist effects on the pacemaker current (If). The aim of this study was to investigate the pharmacological effects of ivabradine on the pulmonary vein (PV) cardiomyocytes. Methods: Whole-cell patch clamp techniques and the indo-1 fluorimetric ratio technique were used to investigate the characteristics of the If and intracellular calcium (Ca2+i) in single isolated rabbit PV cardiomyocytes with pacemaker activity before and after an ivabradine administration (0.3, 3, 10, and 30 μM). Results: Ivabradine concentration-dependently decreased the spontaneous activity and the If in PV cardiomyocytes. The decreased extent of the PV beating rate or If by the different concentrations of ivabradine correlated well with the baseline PV beating rates. The IC50 of the spontaneous activity and If induced by ivabradine were 9.5μM and 3.5μM, respectively. Moreover, ivabradine (30uM, but not 3uM) decreased the Ca2+i transient in the PV cardiomyocytes and ivabradine (30 uM) decreased the L-type calcium current in the PV cardiomyocytes. Conclusion: Ivabradine decreased the pacemaker currents and Ca2+i transient in the PV cardiomyocytes, which may contribute to its inhibitory effects on the PV spontaneous activity.",

keywords = "atrial fibrillation, pacemaker current, pulmonary vein",

author = "Kazuyoshi Suenari and Yukiko Nakano and Yasuki Kihara and Kazuyoshi Suenari and Chen, {Yao Chang} and Chen, {Yi Jen} and Chen, {Shih Ann}",

year = "2011",

doi = "10.4020/jhrs.27.OP23_2",

language = "English",

volume = "27",

pages = "263",

journal = "Journal of Arrhythmia",

issn = "1880-4276",

publisher = "John Wiley & Sons Inc.",

number = "4",

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T1 - Effects of Ivabradine on the Pulmonary Vein Electrical Activity and Modulation of Pacemaker Currents and Calcium Homeostasis

AU - Suenari, Kazuyoshi

AU - Nakano, Yukiko

AU - Kihara, Yasuki

AU - Suenari, Kazuyoshi

AU - Chen, Yao Chang

AU - Chen, Yi Jen

AU - Chen, Shih Ann

PY - 2011

Y1 - 2011

N2 - Introduction: Ivabradine is a novel heart rate decreasing agent with selective and specific antagonist effects on the pacemaker current (If). The aim of this study was to investigate the pharmacological effects of ivabradine on the pulmonary vein (PV) cardiomyocytes. Methods: Whole-cell patch clamp techniques and the indo-1 fluorimetric ratio technique were used to investigate the characteristics of the If and intracellular calcium (Ca2+i) in single isolated rabbit PV cardiomyocytes with pacemaker activity before and after an ivabradine administration (0.3, 3, 10, and 30 μM). Results: Ivabradine concentration-dependently decreased the spontaneous activity and the If in PV cardiomyocytes. The decreased extent of the PV beating rate or If by the different concentrations of ivabradine correlated well with the baseline PV beating rates. The IC50 of the spontaneous activity and If induced by ivabradine were 9.5μM and 3.5μM, respectively. Moreover, ivabradine (30uM, but not 3uM) decreased the Ca2+i transient in the PV cardiomyocytes and ivabradine (30 uM) decreased the L-type calcium current in the PV cardiomyocytes. Conclusion: Ivabradine decreased the pacemaker currents and Ca2+i transient in the PV cardiomyocytes, which may contribute to its inhibitory effects on the PV spontaneous activity.

AB - Introduction: Ivabradine is a novel heart rate decreasing agent with selective and specific antagonist effects on the pacemaker current (If). The aim of this study was to investigate the pharmacological effects of ivabradine on the pulmonary vein (PV) cardiomyocytes. Methods: Whole-cell patch clamp techniques and the indo-1 fluorimetric ratio technique were used to investigate the characteristics of the If and intracellular calcium (Ca2+i) in single isolated rabbit PV cardiomyocytes with pacemaker activity before and after an ivabradine administration (0.3, 3, 10, and 30 μM). Results: Ivabradine concentration-dependently decreased the spontaneous activity and the If in PV cardiomyocytes. The decreased extent of the PV beating rate or If by the different concentrations of ivabradine correlated well with the baseline PV beating rates. The IC50 of the spontaneous activity and If induced by ivabradine were 9.5μM and 3.5μM, respectively. Moreover, ivabradine (30uM, but not 3uM) decreased the Ca2+i transient in the PV cardiomyocytes and ivabradine (30 uM) decreased the L-type calcium current in the PV cardiomyocytes. Conclusion: Ivabradine decreased the pacemaker currents and Ca2+i transient in the PV cardiomyocytes, which may contribute to its inhibitory effects on the PV spontaneous activity.

KW - atrial fibrillation

KW - pacemaker current

KW - pulmonary vein

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Effects of Ivabradine on the Pulmonary Vein Electrical Activity and Modulation of Pacemaker Currents and Calcium Homeostasis

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