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

依瓦布拉定 医学 心脏病学 内科学 平衡 肺静脉 心脏起搏器 心房颤动 心率 血压
作者
Kazuyoshi Suenari,Chen‐Chuan Cheng,YAO‐CHANG CHEN,Yung‐Kuo Lin,Yukiko Nakano,YASUKI KIHARA,Shih‐Ann Chen,Yi‐Jen Chen
出处
期刊:Journal of Cardiovascular Electrophysiology [Wiley]
卷期号:23 (2): 200-206 被引量:42
标识
DOI:10.1111/j.1540-8167.2011.02173.x
摘要

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.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.Ivabradine decreased the I(f)s and Ca(2+)(i) transient in the PV cardiomyocytes, which may contribute to its inhibitory effects on the PV spontaneous activity.
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