Characteristics and Superoxide-Induced Activation of Reconstituted Myocardial Mitochondrial ATP-Sensitive Potassium Channels
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- David X. Zhang
- From the Department of Pharmacology and Toxicology (D.X.Z., Y.-F.C., W.B.C., G.J.G., P.-L.L.) and the Department of Physiology (A.-P.Z.), Medical College of Wisconsin, Milwaukee, Wis.
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- Ya-Fei Chen
- From the Department of Pharmacology and Toxicology (D.X.Z., Y.-F.C., W.B.C., G.J.G., P.-L.L.) and the Department of Physiology (A.-P.Z.), Medical College of Wisconsin, Milwaukee, Wis.
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- William B. Campbell
- From the Department of Pharmacology and Toxicology (D.X.Z., Y.-F.C., W.B.C., G.J.G., P.-L.L.) and the Department of Physiology (A.-P.Z.), Medical College of Wisconsin, Milwaukee, Wis.
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- Ai-Ping Zou
- From the Department of Pharmacology and Toxicology (D.X.Z., Y.-F.C., W.B.C., G.J.G., P.-L.L.) and the Department of Physiology (A.-P.Z.), Medical College of Wisconsin, Milwaukee, Wis.
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- Garrett J. Gross
- From the Department of Pharmacology and Toxicology (D.X.Z., Y.-F.C., W.B.C., G.J.G., P.-L.L.) and the Department of Physiology (A.-P.Z.), Medical College of Wisconsin, Milwaukee, Wis.
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- Pin-Lan Li
- From the Department of Pharmacology and Toxicology (D.X.Z., Y.-F.C., W.B.C., G.J.G., P.-L.L.) and the Department of Physiology (A.-P.Z.), Medical College of Wisconsin, Milwaukee, Wis.
抄録
<jats:p> Mitochondrial ATP-sensitive potassium (mitoK <jats:sub>ATP</jats:sub> ) channels have been suggested as triggers and end effectors in myocardial ischemic preconditioning. However, the intracellular mechanism regulating mitoK <jats:sub>ATP</jats:sub> channels remains unclear. In the present study, mitoK <jats:sub>ATP</jats:sub> channels from bovine ventricular myocardium were reconstituted using planar lipid bilayers, and the effect of superoxide (O <jats:sub>2</jats:sub> <jats:sup>−·</jats:sup> ) on the activity of these reconstituted channels was examined. After incorporation, a potassium-selective current was recorded. The mean conductance of this current was 56 pS at 150 mmol/L KCl, which was substantially inhibited by 1 mmol/L MgATP. 5-Hydroxydecanoate (5-HD, 10 to 100 μmol/L), a selective mitoK <jats:sub>ATP</jats:sub> antagonist, reduced the open state probability (NPo) of these channels in a concentration-dependent manner, whereas diazoxide (10 μmol/L), a selective mitoK <jats:sub>ATP</jats:sub> agonist, significantly increased channel activity. HMR-1098 (100 μmol/L), a selective sarcolemmal K <jats:sub>ATP</jats:sub> antagonist, had no effect on the activity of reconstituted channels. Addition of xanthine/xanthine oxidase (100 μmol/L per 0.038 U/mL), an O <jats:sub>2</jats:sub> <jats:sup>−·</jats:sup> -generating system, resulted in a marked activation of mitoK <jats:sub>ATP</jats:sub> channels; the NPo of the channels was increased from 0.60±0.10 to 1.94±0.02. This O <jats:sub>2</jats:sub> <jats:sup>−·</jats:sup> -induced channel activation was completely abolished by pretreatment with 5-HD (100 μmol/L) or a sulfhydryl alkylating compound, <jats:italic>N</jats:italic> -ethylmaleimide (2 mmol/L). It is concluded that myocardial mitoK <jats:sub>ATP</jats:sub> channels can be reconstituted into lipid bilayers and that O <jats:sub>2</jats:sub> <jats:sup>−·</jats:sup> activates these channels. The effect of O <jats:sub>2</jats:sub> <jats:sup>−·</jats:sup> may be associated with its direct action on the sulfhydryl groups of the channel protein. </jats:p>
収録刊行物
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- Circulation Research
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Circulation Research 89 (12), 1177-1183, 2001-12-07
Ovid Technologies (Wolters Kluwer Health)
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詳細情報 詳細情報について
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- CRID
- 1363388844960116224
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- NII論文ID
- 30029739010
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- ISSN
- 15244571
- 00097330
- http://id.crossref.org/issn/00097330
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- データソース種別
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- Crossref
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