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Inhibitory effects of aprindine on the delayed rectifier K+ current and the muscarinic acetylcholine receptor‐operated K+ current in guinea‐pig atrial cells

Ohmoto‐Sekine, Yuki ; Uemura, Hiroko ; Tamagawa, Masaji ; Nakaya, Haruaki

British journal of pharmacology, 1999-02, Vol.126 (3), p.751-761 [Periódico revisado por pares]

Oxford, UK: Blackwell Publishing Ltd

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Título:
Inhibitory effects of aprindine on the delayed rectifier K+ current and the muscarinic acetylcholine receptor‐operated K+ current in guinea‐pig atrial cells
Autor: Ohmoto‐Sekine, Yuki ; Uemura, Hiroko ; Tamagawa, Masaji ; Nakaya, Haruaki
Assuntos: Action Potentials - drug effects ; Animals ; Anti-Arrhythmia Agents - pharmacology ; Antiarrhythmic drug ; Antiarythmic agents ; aprindine ; Aprindine - pharmacology ; atrial fibrillation ; Atrial Fibrillation - prevention & control ; Atrial Function ; Biological and medical sciences ; Carbachol - pharmacology ; Cardiovascular system ; delayed rectifier K+ current ; Guinea Pigs ; Heart Atria - cytology ; Heart Atria - drug effects ; Medical sciences ; Membrane Potentials - drug effects ; muscarinic acetylcholine receptor‐operated K+ current ; Muscarinic Agonists - pharmacology ; Patch-Clamp Techniques ; Pharmacology. Drug treatments ; Potassium Channels - drug effects ; Receptors, Muscarinic - physiology ; Time Factors
É parte de: British journal of pharmacology, 1999-02, Vol.126 (3), p.751-761
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: In order to clarify the mechanisms by which the class Ib antiarrhythmic drug aprindine shows efficacy against atrial fibrillation (AF), we examined the effects of the drug on the repolarizing K+ currents in guinea‐pig atrial cells by use of patch‐clamp techniques. We also evaluated the effects of aprindine on experimental AF in isolated guinea‐pig hearts. Aprindine (3 μM) inhibited the delayed rectifier K+ current (IK) with little influence on the inward rectifier K+ current (IK1) or the Ca2+ current. Electrophysiological analyses including the envelope of tails test revealed that aprindine preferentially inhibits IKr (rapidly activating component) but not IKs (slowly activating component). The muscarinic acetylcholine receptor‐operated K+ current (IK.ACh) was activated by the extracellular application of carbachol (1 μM) or by the intracellular loading of GTPγS. Aprindine inhibited the carbachol‐ and GTPγS‐induced IK.ACh with the IC50 values of 0.4 and 2.5 μM, respectively. In atrial cells stimulated at 0.2 Hz, aprindine (3 μM) per se prolonged the action potential duration (APD) by 50±4%. The drug also reversed the carbachol‐induced action potential shortening in a concentration‐dependent manner. In isolated hearts, perfusion of carbachol (1 μM) shortened monophasic action potential (MAP) and effective refractory period (ERP), and lowered atrial fibrillation threshold. Addition of aprindine (3 μM) inhibited the induction of AF by prolonging MAP and ERP. We conclude the efficacy of aprindine against AF may be at least in part explained by its inhibitory effects on IKr and IK.ACh. British Journal of Pharmacology (1999) 126, 751–761; doi:10.1038/sj.bjp.0702334
Editor: Oxford, UK: Blackwell Publishing Ltd
Idioma: Inglês

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Inhibitory effects of aprindine on the delayed rectifier K+ current and the muscarinic acetylcholine receptor‐operated K+ current in guinea‐pig atrial cells

Ohmoto‐Sekine, Yuki ; Uemura, Hiroko ; Tamagawa, Masaji ; Nakaya, Haruaki

Oxford, UK: Blackwell Publishing Ltd

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