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01-07-2016 | Original Article

Short- and long-term inhibition of cardiac inward-rectifier potassium channel current by an antiarrhythmic drug bepridil

Authors: Fangfang Ma, Hiroki Takanari, Kimiko Masuda, Masaki Morishima, Katsushige Ono

Published in: Heart and Vessels | Issue 7/2016

Abstract

Bepridil is an effective antiarrhythmic drug on supraventricular and ventricular arrhythmias, and inhibitor of calmodulin. Recent investigations have been elucidating that bepridil exerts antiarrhythmic effects through its acute and chronic application for patients. The aim of this study was to identify the efficacy and the potential mechanism of bepridil on the inward-rectifier potassium channel in neonatal rat cardiomyocytes in acute- and long-term conditions. Bepridil inhibited inward-rectifier potassium current (I _K1) as a short-term effect with IC₅₀ of 17 μM. Bepridil also reduced I _K1 of neonatal cardiomyocytes when applied for 24 h in the culture medium with IC₅₀ of 2.7 μM. Both a calmodulin inhibitor (W-7) and an inhibitor of calmodulin-kinase II (KN93) reduced I _K1 when applied for 24 h as a long-term effect in the same fashion, suggesting that the long-term application of bepridil inhibits I _K1 more potently than that of the short-term application through the inhibition of calmodulin kinase II pathway in cardiomyocytes.

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Title: Short- and long-term inhibition of cardiac inward-rectifier potassium channel current by an antiarrhythmic drug bepridil
Authors: Fangfang Ma
Hiroki Takanari
Kimiko Masuda
Masaki Morishima
Katsushige Ono
Publication date: 01-07-2016
Publisher: Springer Japan
Published in: Heart and Vessels / Issue 7/2016
Print ISSN: 0910-8327
Electronic ISSN: 1615-2573
DOI: https://doi.org/10.1007/s00380-015-0762-1

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