当前位置： SCI文献检索 > JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY期刊下所有文献 > The heart rate-lowering agent ivabradine inhibits the pacemaker current I(f) in human atrial myocytes.

The heart rate-lowering agent ivabradine inhibits the pacemaker current I(f) in human atrial myocytes.

Abstract：

INTRODUCTION:It has been speculated that pacemaker current (I(f)) in human atria could play a role in causing ectopic atrial automaticity. Ivabradine is a novel selective and specific I(f) inhibitor in the sinus node that reduces heart rate without any negative inotropic effect. The aim of the study was to explore possible effects of ivabradine on I(f) in atrial myocytes. METHODS AND RESULTS:Using patch-clamp technique, we studied effects of ivabradine on I(f) present in atrial myocytes isolated from human right appendages of patients undergoing cardiac surgery. The identification of HCN isoforms was obtained by means of multiplex single-cell RT-PCR. Ivabradine induced a marked concentration and use-dependent I(f) inhibition with an IC50 at steady state of 2.9 microM. Time constant of block development (Tau(on)) decreases with the increase in the ivabradine concentration. Use-dependent inhibition induced by ivabradine (3 microM) was not modified in the presence of cAMP (10 microM) in the pipette solution. Multiplex single-cell RT-PCR indicates that the major HCN gene subtype detected in atria was HCN2. HCN4 is detected weakly and HCN1 is not significantly detected. CONCLUSIONS:Ivabradine inhibits I(f) current in the nonpacemaker cell with characteristics similar to those described previously in rabbit sinus node cells, but revealed a lesser sensitivity for I(f) recorded in human atrial cell than hHCN4 subunits considered as the major contributors to native f-channels in human sinoatrial node. A potential protection of atrial arrhythmias by ivabradine is discussed.

journal_name

J Cardiovasc Electrophysiol

journal_title

Journal of cardiovascular electrophysiology

authors

El Chemaly A,Magaud C,Patri S,Jayle C,Guinamard R,Bois P

doi

10.1111/j.1540-8167.2007.00955.x

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

1190-6

issue

11

eissn

1045-3873

issn

1540-8167

pii

JCE955

journal_volume

18

pub_type

杂志文章

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