Short- and long-term inhibition of cardiac inward-rectifier potassium channel current by an antiarrhythmic drug bepridil.
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.
Department of Pathophysiology, Oita University School of Medicine, Yufu, 879-5593, Oita, Japan.|Department of Cardiology, The 1st Hospital of Hebei Medical University, Shijiazhung, 050031, Hebei, China.
Fangfang
F
Ma
Department of Pathophysiology, Oita University School of Medicine, Yufu, 879-5593, Oita, Japan.
Hiroki
H
Takanari
Department of Pathophysiology, Oita University School of Medicine, Yufu, 879-5593, Oita, Japan.
Kimiko
K
Masuda
Department of Pathophysiology, Oita University School of Medicine, Yufu, 879-5593, Oita, Japan.
Masaki
M
Morishima
Department of Pathophysiology, Oita University School of Medicine, Yufu, 879-5593, Oita, Japan. ono@oita-u.ac.jp.
Katsushige
K
Ono
D000818:Animals; D000831:Animals, Newborn; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology; D015764:Bepridil / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D008564:Membrane Potentials; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D000096926:Benzenesulfonamides
D000889:Anti-Arrhythmia Agents; D001596:Benzylamines; D015764:Bepridil; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002147:Calmodulin; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides; C017967:W 7
Bepridil; Calmodulin; Inward-rectifier K+ channel; KN93; W-7