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

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概要

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• 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.

• 社団法人 日本薬理学会の論文
• 2009-06-20

著者

• MIYAZAKI Masaru

  Department of General Surgery, Chiba University Graduate School of Medicine

• NAKAYA Haruaki

  Department of Pharmacology, Chiba University Graduate School of Medicine

• KOMURO Issei

  Chiba University

• Nagai Toshio

  Department of Cardiovascular Science and Medicine, Chiba University graduate School of Medicine

• Komuro Issei

  Department of Cardiovascular Science and Medicine, Chiba University graduate School of Medicine

• Komuro I

  Chiba University

• Komura Issei

  Department Of Cardiovascular Science And Medicine Chiba University Graduate School Of Medicine

• Nakaya Haruaki

  神戸大学 医学部

• OGURA Takehiko

  Department of Pharmacology, Chiba University Graduate School of Medicine

• Komuro I

  Department Of Cardiovascular Science And Medicine Chiba University Graduate School Of Medicine

• Nagai T

  Department Of Cardiovascular Science And Medicine Chiba University Graduate School Of Medicine

• Ogura Takehiko

  Dep. Of Pharmacology Chiba Univ. Graduate School Of Medicine Jpn

• Ogura Takehiko

  Department Of Pharmacology Chiba University Graduate School Of Medicine

• Nakaya Haruaki

  慶応義塾大学 医学部

• Nagai Toshio

  Dep. Of Cardiovascular Sci. And Medicine Chiba Univ. Graduate School Of Medicine Jpn

• Nagai Toshio

  Department Of Cardiovascular Science And Medicine Chiba University Graduate School Of Medicine

• TAMURA Atsushi

  Department of Pharmacology, Chiba University Graduate School of Medicine

• UEMURA Hiroko

  Department of Pharmacology, Chiba University Graduate School of Medicine

• REIEN Yoshie

  Department of Pharmacology, Chiba University Graduate School of Medicine

• KISHIMOTO Takashi

  Department of Molecular Pathology, Chiba University Graduate School of Medicine

• Nakaya Haruaki

  Department Of Orthopaedic Surgery And Pharmacology School Of Medicine Chiba University

• Uemura Hiroko

  Department Of Pharmacology Chiba University Graduate School Of Medicine

• Komuro Issei

  Department Of Cardiovascular Science And Medicine Chiba University Graduate School Of Medicine

• Komuro Issei

  Department Of Cardiovascular Medicine Chiba University School Of Medicine

• Nakaya Haruaki

  Department Of Pharmacology Chiba University School Of Medicine

• Miyazaki Masaru

  Department Of General Surgery Chiba University Graduate School Of Medicine

• Tamura Atsushi

  Department Of Applied Chemistry Faculty Of Science Tokyo University Of Science

• Tamura Atsushi

  Department Of Pharmacology Chiba University Graduate School Of Medicine

• Kishimoto Takashi

  Department Of Chemical Science And Engineering Kobe University

• Reien Yoshie

  Department Of Pharmacology Chiba University Graduate School Of Medicine

• Miyazaki Masaru

  Department Of General Surgery Chiba University

• Komuro Issei

  Department Of Cardiovascularr Science And Medicine Chiba University Graduate School Of Medicine

• Komuro Issei

  Department Of Cardiovascular Science And Medicine Chiba University

• Komuro0 Issei

  The Third Department Of Internal Medicine Faculty Of Medicine University Of Tokyo

• Komuro Issei

  Department Of Cardiovascular Science And Medicine Chiba University Graduate School Of Medicine (m4)

• Komuro Issei

  The Third Department Of Internal Medicine Faculty Of Medicine University Of Tokyo

• Komuro Issei

  Department Of Cardiovascular Medicine

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