Effects of Ivabradine on the Pulmonary Vein Electrical Activity and Modulation of Pacemaker Currents and Calcium Homeostasis
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概要
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<B>Introduction:</B> Ivabradine is a novel heart rate decreasing agent with selective and specific antagonist effects on the pacemaker current (I<SUB>f</SUB>). The aim of this study was to investigate the pharmacological effects of ivabradine on the pulmonary vein (PV) cardiomyocytes. <B>Methods:</B> Whole-cell patch clamp techniques and the indo-1 fluorimetric ratio technique were used to investigate the characteristics of the I<SUB>f</SUB> and intracellular calcium (Ca<SUP>2+</SUP><SUB>i</SUB>) in single isolated rabbit PV cardiomyocytes with pacemaker activity before and after an ivabradine administration (0.3, 3, 10, and 30 µM). <B>Results:</B> Ivabradine concentration-dependently decreased the spontaneous activity and the I<SUB>f</SUB> in PV cardiomyocytes. The decreased extent of the PV beating rate or I<SUB>f</SUB> by the different concentrations of ivabradine correlated well with the baseline PV beating rates. The IC<SUB>50</SUB> of the spontaneous activity and I<SUB>f</SUB> induced by ivabradine were 9.5 µM and 3.5 µM, respectively. Moreover, ivabradine (30 µM, but not 3 µM) decreased the Ca<SUP>2+</SUP><SUB>i</SUB> transient in the PV cardiomyocytes and ivabradine (30 µM) decreased the L-type calcium current in the PV cardiomyocytes. <B>Conclusion:</B> Ivabradine decreased the pacemaker currents and Ca<SUP>2+</SUP><SUB>i</SUB> transient in the PV cardiomyocytes, which may contribute to its inhibitory effects on the PV spontaneous activity.
著者
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Chen Shih-ann
Division Of Cardiology Department Of Medicine And National Yang-ming University School Of Medicine A
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Chen Yi-jen
Division Of Cardiovascular Medicine Taipei Medical University-wan-fang Hospital And School Of Medici
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Suenari Kazuyoshi
Department Of Cardiology Hiroshima University School Of Medicine
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Kihara Yasuki
Department Of Cardiology Graduate School Of Medicine Kyoto University
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Nakano Yukiko
Department Of Biostructural Science Graduate School Of Tokyo Medical And Dental University
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Nakano Yukiko
Department of Cardiovascular Medicine, Hiroshima University Hospital
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Chen Yao-Chang
Division of Cardiology, Taipei Veterans General Hospital
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Chen Shih-Ann
Division of Cardiology and Cardiovascular Research Center, National Yang-Ming University, School of Medicine, and Taipei Veterans General Hospital, Taipei Municipal Gan-Dau Hospital
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Chen Yi-Jen
Division of Cardiology, Taipei Veterans General Hospital
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Suenari Kazuyoshi
Department of Cardiovascular Medicine, Hiroshima University Hospital
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