Effects of Antiarrhythmic Drugs on the Hyperpolarization-Activated Cyclic Nucleotide–Gated Channel Current

Journal of Pharmacological Sciences

Issei Komuro¹  Toshio Nagai¹  Yoshie Reien⁴  Atsushi Tamura⁴  Haruaki Nakaya⁴  Masaru Miyazaki³  Hiroko Uemura⁴  Takehiko Ogura⁴  Takashi Kishimoto² 

[1] Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Japan;Department of Molecular Pathology, Chiba University Graduate School of Medicine, Japan;Department of General Surgery, Chiba University Graduate School of Medicine, Japan;Department of Pharmacology, Chiba University Graduate School of Medicine, Japan

关键词: antiarrhythmic drug;    hyperpolarization-activated cyclic nucleotide–gated (HCN) channel subtype 4;    pacemaker current;    amiodarone;    bepridil;   

DOI  :  10.1254/jphs.08312FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(33)Cited-By(16)After the report of the Cardiac Arrhythmia Suppression Trial, a tabular framework of the Sicilian Gambit has been proposed to display actions of antiarrhythmic drugs on ion channels and receptors and to provide more rational pharmacotherapy of arrhythmias. However, because effects of antiarrhythmic drugs on If have not been thoroughly examined, we used patch clamp techniques to determine the effects of various antiarrhythmic drugs on the HCN (hyperpolarization-activated cyclic nucleotide–gated) channel currents. HCN4 channels, a dominant isoform of HCN channels in the heart, were expressed in HEK293 cells. Amiodarone and bepridil potently inhibited the HCN4 channel current with IC50 values of 4.5 and 4.9 μM, respectively, which were close to their therapeutic concentrations. The inhibitory effects of quinidine, disopyramide, cibenzoline, lidocaine, mexiletine, aprindine, propafenone, flecainide, propranolol, and verapamil on the HCN4 channel current were weak in their therapeutic concentrations, with IC50 values of 78.3, 249, 46.8, 276, 309, 43.7, 14.3, 1700, 50.5, and 44.9 μM, respectively, suggesting that the inhibitory effects on If would be clinically small. d,l-Sotalol hardly affected the HCN4 channel current. Information about the HCN4-channel effects of many antiarrhythmic drugs may be useful for determining the appropriate drug for treatment of various arrhythmias while minimizing adverse effects.

【 授权许可】

Unknown