Source:http://linkedlifedata.com/resource/pubmed/id/11701616
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
2001-11-9
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| pubmed:abstractText |
Mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels play a key role in ischemic preconditioning of the heart. However, the mechanism of cardioprotection remains controversial. We measured rhod-2 fluorescence in adult rabbit ventricular cardiomyocytes as an index of mitochondrial matrix Ca(2+) concentration ([Ca(2+)](m)), using time-lapse confocal microscopy. To simulate ischemia and reperfusion (I/R), cells were exposed to metabolic inhibition (50 minutes) followed by washout with control solution. Rhod-2 fluorescence gradually increased during simulated ischemia and rose even further with reperfusion. The mitoK(ATP) channel opener diazoxide attenuated the accumulation of [Ca(2+)](m) during simulated I/R (EC(50)=18 micromol/L). These effects of diazoxide were blocked by the mitoK(ATP) channel antagonist 5-hydroxydecanoate (5HD). In contrast, inhibitors of the mitochondrial permeability transition (MPT), cyclosporin A and bongkrekic acid, did not alter [Ca(2+)](m) accumulation during ischemia, but markedly suppressed the surge in rhod-2 fluorescence during reperfusion. Measurements of mitochondrial membrane potential, DeltaPsi(m), in permeabilized myocytes revealed that diazoxide depolarized DeltaPsi(m) (by 12% at 10 micromol/L, P<0.01) in a 5HD-inhibitable manner. Our data support the hypothesis that attenuation of mitochondrial Ca(2+) overload, as a consequence of partial mitochondrial membrane depolarization by mitoK(ATP) channels, underlies cardioprotection. Furthermore, mitoK(ATP) channels and the MPT differentially affect mitochondrial calcium homeostasis: mitoK(ATP) channels suppress calcium accumulation during I/R, while the MPT comes into play only upon reperfusion.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5-hydroxydecanoic acid,
http://linkedlifedata.com/resource/pubmed/chemical/Bongkrekic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Decanoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Diazoxide,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescent Dyes,
http://linkedlifedata.com/resource/pubmed/chemical/Heterocyclic Compounds, 3-Ring,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxy Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/mitochondrial K(ATP) channel,
http://linkedlifedata.com/resource/pubmed/chemical/rhod-2
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
1524-4571
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
9
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| pubmed:volume |
89
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
891-8
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:11701616-Bongkrekic Acid,
pubmed-meshheading:11701616-Calcium,
pubmed-meshheading:11701616-Cell Separation,
pubmed-meshheading:11701616-Cytoprotection,
pubmed-meshheading:11701616-Decanoic Acids,
pubmed-meshheading:11701616-Diazoxide,
pubmed-meshheading:11701616-Dose-Response Relationship, Drug,
pubmed-meshheading:11701616-Fluorescent Dyes,
pubmed-meshheading:11701616-Heterocyclic Compounds, 3-Ring,
pubmed-meshheading:11701616-Hydroxy Acids,
pubmed-meshheading:11701616-Intracellular Membranes,
pubmed-meshheading:11701616-Ischemic Preconditioning,
pubmed-meshheading:11701616-Membrane Proteins,
pubmed-meshheading:11701616-Microscopy, Confocal,
pubmed-meshheading:11701616-Microscopy, Fluorescence,
pubmed-meshheading:11701616-Mitochondria,
pubmed-meshheading:11701616-Myocardial Ischemia,
pubmed-meshheading:11701616-Myocardial Reperfusion,
pubmed-meshheading:11701616-Myocardium,
pubmed-meshheading:11701616-Permeability,
pubmed-meshheading:11701616-Potassium Channels
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| pubmed:year |
2001
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| pubmed:articleTitle |
Mitochondrial ATP-sensitive potassium channels attenuate matrix Ca(2+) overload during simulated ischemia and reperfusion: possible mechanism of cardioprotection.
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| pubmed:affiliation |
Institute of Molecular Cardiobiology, The Johns Hopkins University, Baltimore, MD, USA.
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| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|