Characteristics and Superoxide-Induced Activation of Reconstituted Myocardial Mitochondrial ATP-Sensitive Potassium Channels

• 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.

• 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.

• 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.

• 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.

• 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.

• 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

Mitochondrial ATP-sensitive potassium (mitoK ATP ) channels have been suggested as triggers and end effectors in myocardial ischemic preconditioning. However, the intracellular mechanism regulating mitoK ATP channels remains unclear. In the present study, mitoK ATP channels from bovine ventricular myocardium were reconstituted using planar lipid bilayers, and the effect of superoxide (O 2 −· ) 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 ATP antagonist, reduced the open state probability (NPo) of these channels in a concentration-dependent manner, whereas diazoxide (10 μmol/L), a selective mitoK ATP agonist, significantly increased channel activity. HMR-1098 (100 μmol/L), a selective sarcolemmal K ATP 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 2 −· -generating system, resulted in a marked activation of mitoK ATP channels; the NPo of the channels was increased from 0.60±0.10 to 1.94±0.02. This O 2 −· -induced channel activation was completely abolished by pretreatment with 5-HD (100 μmol/L) or a sulfhydryl alkylating compound, N -ethylmaleimide (2 mmol/L). It is concluded that myocardial mitoK ATP channels can be reconstituted into lipid bilayers and that O 2 −· activates these channels. The effect of O 2 −· may be associated with its direct action on the sulfhydryl groups of the channel protein.

収録刊行物

• Circulation Research

  Circulation Research 89 (12), 1177-1183, 2001-12-07

  Ovid Technologies (Wolters Kluwer Health)

キーワード

• Cardiology and Cardiovascular Medicine
• Physiology

詳細情報

• CRID: 1363388844960116224
• NII論文ID: 30029739010
• DOI: 10.1161/hh2401.101752
• ISSN: 15244571
• ISSN: 00097330
• ISSN: http://id.crossref.org/issn/00097330
• Web Site: https://www.ahajournals.org/doi/full/10.1161/hh2401.101752
• データソース種別:
  • Crossref
  • CiNii Articles