Effects of Azimilide on the Muscarinic Acetylcholine Receptor-Operated K^+ Current and Experimental Atrial Fibrillation in Guinea-Pig Hearts
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概要
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Effects of azimilide, a class III antiarrhythmic drug, on the acetylcholine (ACh) receptor-operated K+ current (IK.ACh) and the delayed rectifier K+ current (IK) were examined in guinea-pig atrial cells using patch-clamp techniques. Effects of azimilide on experimental atrial fibrillation (AF) were also examined in isolated guinea-pig hearts. In single atrial myocytes, azimilide inhibited both the rapid (IKr) and slow component of IK (IKs). Azimilide inhibited the IK.ACh induced by carbachol (CCh, 1 μM), adenosine (10 μM), and intracellular loading of GTPγS (100 μM) in a concentration-dependent manner. The IC50 values of azimilide for inhibiting the CCh-, adenosine-, and GTPγS-induced IK.ACh were 1.25, 29.1, and 20.9 μM, respectively, suggesting that azimilide inhibits IK.ACh mainly by blocking the muscarinic receptors. Azimilide concentration-dependently (0.3 – 10 μM) prolonged the action potential duration (APD) in the absence and presence of muscarinic stimulation. In isolated hearts, perfusion of CCh shortened the duration of the monophasic action potential (MAP) and effective refractory period (ERP) of the left atrium and lowered the atrial fibrillation threshold (AFT). Addition of azimilide inhibited the induction of AF by prolonging the duration of MAP and ERP. The IK.ACh inhibition by azimilide may at least in part contribute to the effectiveness to prevent parasympathetic-type AF.
- 社団法人 日本薬理学会の論文
- 2007-11-20
著者
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NAKAYA Haruaki
Department of Pharmacology, Chiba University Graduate School of Medicine
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Tamagawa Masaji
Department of Pharmacology, Chiba University Graduate School of Medicine
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Nakaya Haruaki
神戸大学 医学部
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OGURA Takehiko
Department of Pharmacology, Chiba University Graduate School of Medicine
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NISHIDA Atsushi
Department of Psychiatry, Division of Neuroscience, Mie University, Graduate School of Medicine
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Tamagawa Masaji
千葉大学 循環病態医科学
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Tamagawa Masaji
Department Of Pharmacology Chiba University Graduate School Of Medicine
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Ogura Takehiko
Dep. Of Pharmacology Chiba Univ. Graduate School Of Medicine Jpn
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Ogura Takehiko
Department Of Pharmacology Chiba University Graduate School Of Medicine
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Nakaya Haruaki
慶応義塾大学 医学部
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UEMURA Hiroko
Department of Pharmacology, Chiba University Graduate School of Medicine
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REIEN Yoshie
Department of Pharmacology, Chiba University Graduate School of Medicine
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Nakaya Haruaki
Department Of Orthopaedic Surgery And Pharmacology School Of Medicine Chiba University
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Uemura Hiroko
Department Of Pharmacology Chiba University Graduate School Of Medicine
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Yabana Hideo
Discovery Research Laboratory, Tanabe Seiyaku, Co.
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Nakaya Haruaki
Department Of Pharmacology Chiba University School Of Medicine
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Yabana Hideo
Discovery And Pharmacology Research Laboratories Tanabe Seiyaku Co. Ltd.
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Nishida Atsushi
Lab. Of Organic Chemistry Graduate School Of Pharmaceutical Sciences Chiba Univ. Jpn
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Nishida Atsushi
Department Of Chemical System Engineering The University Of Tokyo
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Ogura Takehiko
Department Of Pharmacology Chiba University School Of Medicine
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Reien Yoshie
Department Of Pharmacology Chiba University Graduate School Of Medicine
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Nishida Atsushi
Department Of Pharmacology Chiba University Graduate School Of Medicine
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