Effects of ivabradine on the pulmonary vein electrical activity and modulation of pacemaker currents and calcium homeostasis

Yao Chang Chen, Kazuyoshi Suenari, Chen Chuan Cheng, Yung Kuo Lin, Yukiko Nakano, Yasuki Kihara, Shih Ann Chen, Yi Jen Chen

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44 Citations (Scopus)


Effects of Ivabradine on Pulmonary Veins. Introduction: Ivabradine is a novel heart rate decreasing agent with selective and specific antagonist effects on the pacemaker current (I f). The aim of this study was to investigate the pharmacological effects of ivabradine on the pulmonary vein (PV) cardiomyocytes. Methods and Results: Whole-cell patch-clamp techniques and the indo-1 fluorimetric ratio technique were used to investigate the characteristics of the I f and intracellular calcium (Ca 2+ i) in single isolated rabbit PV cardiomyocytes with pacemaker activity before and after an ivabradine administration (0.3, 3, 10, and 30 μM). Ivabradine (0.3, 3, 10, and 30 μM) concentration dependently decreased the spontaneous activity by 6 ± 3%, 32 ± 6%, 49 ± 5%, and 85 ± 4%, and decreased the I f by 35 ± 8%, 47 ± 9%, 62 ± 5%, and 65 ± 7%, respectively, in PV cardiomyocytes. The decreased extent of the PV beating rate or I f by the different concentrations of ivabradine correlated well with the baseline PV beating rates. The IC 50 of the spontaneous activity and I f induced by ivabradine were 9.5 and 3.5 μM, respectively. Moreover, ivabradine (30 μM, but not 3 μM) decreased the Ca 2+ i transient in the PV cardiomyocytes and ivabradine (30 μM) decreased the L-type calcium current in the PV cardiomyocytes. Conclusion: Ivabradine decreased the I fs and Ca 2+ i transient in the PV cardiomyocytes, which may contribute to its inhibitory effects on the PV spontaneous activity.

Original languageEnglish
Pages (from-to)200-206
Number of pages7
JournalJournal of Cardiovascular Electrophysiology
Issue number2
Publication statusPublished - Feb 2012


  • atrial fibrillation
  • calcium regulation
  • ivabradine
  • pacemaker current
  • pulmonary vein

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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