(Circulation. 2000;101:439.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Activation of Mitochondrial ATP-Dependent Potassium Channels by Nitric Oxide
From the Institute of Molecular Cardiobiology, Johns Hopkins University, Baltimore, Md.
Correspondence to Eduardo Marbán, MD, PhD, Director, Institute of Molecular Cardiobiology, 844 Ross Bldg, The Johns Hopkins University School of Medicine, Baltimore MD 21205. E-mail marban{at}jhmi.edu
Background—Nitric oxide (NO) has been implicated as a mediator of "second-window" ischemic preconditioning, and mitochondrial ATP-dependent K+ (mitoKATP) channels are the likely effectors. The links between NO and mitoKATP channels are unknown.
Methods and Results—We measured mitochondrial redox potential as an index of mitoKATP channel opening in rabbit ventricular myocytes. The NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP, 0.1 to 1 mmol/L) oxidized the mitochondrial matrix dose-dependently without activating sarcolemmal KATP channels. SNAP-induced oxidation was blocked by the selective mitoKATP channel blocker 5-hydroxydecanoate and by the NO scavenger 2-(4-carboxyphenyl)-4,4',5,5'-tetramethylimidazole-1-oxyl-3-oxide. SNAP-induced mitochondrial oxidation was detectable either by photomultiplier tube recordings of flavoprotein fluorescence or by confocal imaging. SNAP also enhanced the oxidative effects of diazoxide when both agents were applied together. Exposure to 1 mmol/L 8Br-cGMP failed to mimic the effects of SNAP.
Conclusions—NO directly activates mitoKATP channels and potentiates the ability of diazoxide to open these channels. These results provide novel mechanistic links between NO-induced cardioprotection and mitoKATP channels.
Key Words: ischemic preconditioning • nitric oxide • myocytes • mitochondria
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|
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|
|
|
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|
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|
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|
|
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|
|
|
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|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 A. Schwingshackl, R. Moqbel, and M. Duszyk Nitric oxide activates ATP-dependent K+ channels in human eosinophils J. Leukoc. Biol., May 1, 2002; 71(5): 807 - 812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
R. Schulz, M. V Cohen, M. Behrends, J. M Downey, and G. Heusch Signal transduction of ischemic preconditioning Cardiovasc Res, November 1, 2001; 52(2): 181 - 198. [Full Text] [PDF]
|
|
|
|
 |
|
 R D Rakhit and M S Marber Nitric oxide: an emerging role in cardioprotection? Heart, October 1, 2001; 86(4): 368 - 372. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 S. Krick, O. Platoshyn, M. Sweeney, H. Kim, and J. X.-J. Yuan Activation of K+ channels induces apoptosis in vascular smooth muscle cells Am J Physiol Cell Physiol, April 1, 2001; 280(4): C970 - C979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 B. O'Rourke Pathophysiological and protective roles of mitochondrial ion channels J. Physiol., November 15, 2000; 529(1): 23 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|