Opening of Mitochondrial K _ATP Channels Attenuates the Ouabain-Induced Calcium Overload in Mitochondria

• Hideyuki Ishida

  From the Department of Physiology (H.I., Y.H., C.G., H. Nakazawa), Tokai University School of Medicine, Isehara, Japan; Department of Pharmacology (H. Nakaya, T.S.), Graduate School of Medicine, Chiba University, Chiba, Japan.

• Yuki Hirota

  From the Department of Physiology (H.I., Y.H., C.G., H. Nakazawa), Tokai University School of Medicine, Isehara, Japan; Department of Pharmacology (H. Nakaya, T.S.), Graduate School of Medicine, Chiba University, Chiba, Japan.

• Chokoh Genka

  From the Department of Physiology (H.I., Y.H., C.G., H. Nakazawa), Tokai University School of Medicine, Isehara, Japan; Department of Pharmacology (H. Nakaya, T.S.), Graduate School of Medicine, Chiba University, Chiba, Japan.

• Hiroe Nakazawa

  From the Department of Physiology (H.I., Y.H., C.G., H. Nakazawa), Tokai University School of Medicine, Isehara, Japan; Department of Pharmacology (H. Nakaya, T.S.), Graduate School of Medicine, Chiba University, Chiba, Japan.

• Haruaki Nakaya

  From the Department of Physiology (H.I., Y.H., C.G., H. Nakazawa), Tokai University School of Medicine, Isehara, Japan; Department of Pharmacology (H. Nakaya, T.S.), Graduate School of Medicine, Chiba University, Chiba, Japan.

• Toshiaki Sato

  From the Department of Physiology (H.I., Y.H., C.G., H. Nakazawa), Tokai University School of Medicine, Isehara, Japan; Department of Pharmacology (H. Nakaya, T.S.), Graduate School of Medicine, Chiba University, Chiba, Japan.

抄録

We tested whether opening of mitochondrial ATP-sensitive K + (mitoK ATP ) channels depolarizes mitochondrial membrane potential (ΔΨ m ) and thereby prevents the mitochondrial Ca 2+ overload. With the use of a Nipkow disk confocal system, the mitochondrial Ca 2+ concentration ([Ca 2+ ] m ) and ΔΨ m in rat ventricular myocytes were measured by loading cells with Rhod-2 and JC-1, respectively. Exposure to ouabain (1 mmol/L) for 30 minutes produced mitochondrial Ca 2+ overload, and the intensity of Rhod-2 fluorescence significantly increased to 173±16% of baseline ( P <0.001). Treatment of myocytes with the mitoK ATP channel opener diazoxide (100 μmol/L) blunted the ouabain-induced mitochondrial Ca 2+ overload (131±10% of baseline; P <0.001 versus ouabain). Moreover, diazoxide significantly depolarized the ΔΨ m and reduced the intensity of JC-1 fluorescence during application of ouabain to 89±2% of baseline ( P <0.05). These effects of diazoxide were blocked by the mitoK ATP channel blocker 5-hydroxydecanoate (500 μmol/L). These results indicate that opening of mitoK ATP channels prevents a mitochondrial Ca 2+ overload in association with ΔΨ m depolarization and thereby protects myocardium against ischemic damage.

収録刊行物

• Circulation Research

  Circulation Research 89 (10), 856-858, 2001-11-09

  Ovid Technologies (Wolters Kluwer Health)

キーワード

• Cardiology and Cardiovascular Medicine
• Physiology

詳細情報

• CRID: 1360574093940732288
• NII論文ID: 30029739158
• DOI: 10.1161/hh2201.100341
• ISSN: 15244571
• ISSN: 00097330
• ISSN: http://id.crossref.org/issn/00097330
• Web Site: https://www.ahajournals.org/doi/full/10.1161/hh2201.100341
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  • CiNii Articles