Effects of K^+ Channel Modulators on the Relationship Between Action Potential Duration and Ca^<2+> Transients in Single Ventricular Myocytes of the Guinea Pig
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概要
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Effects of K+ channel modulators, cromakalim and E4031 [1-[2-(6-methyl-2-pyridyl)-ethyl]-4-(4-methylsulfonylaminobenzoyl) piperidine], on the relationship between the action potential duration (APD) and Ca2+ transients were examined in single myocytes isolated from guinea pig cardiac left ventricle. Application of cromakalim decreased APD at 90% repolarization (APD90) and Ca2+ transient elicited at 0.5 Hz (IC50s=0.6 and 3 μM, respectively). Application of 0.3 μM E4031 increased these parameters by 110% and 45%, respectively. Under voltage-clamp, the relation between the duration of depolarization to 0 mV and Ca2+ transients could be described by the sum of two exponential components; the time constants were approximately 5 and 280 msec, respectively. The first component was abolished by 10 μM ryanodine, suggesting the involvement of Ca2+-induced Ca2+ release (CICR). Neither cromakalim nor E4031 directly affected Ca2+ current and Ca2+ transients under voltage clamp. When APD was changed by K+ channel modulators, the relation between APD90 and Ca2+-transients was almost similar to that obtained by changing the depolarization duration under voltage-clamp. CICR was changed significantly only when APD90 was markedly shortened by cromakalim. The extensively prolonged AP and Ca2+ transient in the presence of E4031 were reduced by an addition of cromakalim. It is concluded that these two K+ channel modulators can significantly alter the AP-induced Ca2+ transient mainly by changing APD, which regulates both Ca2+ influx and extrusion.
- 社団法人 日本薬理学会の論文
著者
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村木 克彦
名古屋市大・院・細胞分子薬効解析
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Muraki Katsuhiko
Department Of Cellular Pharmacology School Of Pharmacy Aichi-gakuin University
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村木 克彦
Department Of Cellular Pharmacology School Of Pharmacy Aichi-gakuin University
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Imaizumi Y
Dep. Of Molecular And Cellular Pharmacology Graduate School Of Pharmaceutical Sciences Nagoya City U
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Imaizumi Yuji
Department Of Chemical Pharmacolgy Faculty Of Pharmaceutical Sciences Nagoya City University
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Watanabe Minoru
Department Of Molecular And Cellular Pharmacology Nagoya City University
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TOKUNO Tomoaki
Department of Pharmacology & Therapiutics, Faculty of Pharmaceutical Sciences, Nagoya City Universit
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Tokuno Tomoaki
Department Of Pharmacology & Therapiutics Faculty Of Pharmaceutical Sciences Nagoya City Univers
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Ishii Yatsuka
Department Of Clinical Pharmacology And Therapeutics Oita Medical University
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Watanabe Minoru
Department Of Chemical Pharmacolgy Faculty Of Pharmaceutical Sciences Nagoya City University
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Watanabe M
Department Of Molecular And Cellular Pharmacology Faculty Of Pharmaceutical Sciences Nagoya City Uni
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