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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2004-3-18
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pubmed:abstractText |
1. The opening of cardiac plasma-membrane ATP-sensitive K(+) channels (pmK(ATP)) can protect the heart against ischaemia/reperfusion injury. We recently demonstrated that the resting membrane potential (E(m)) of ventricular myocytes strongly modulates reoxygenation-induced Ca(2+) overload. This led to the hypothesis that activation of pmK(ATP) can influence the extent of chemically induced hypoxia (CIH)/reoxygenation Ca(2+) overload via hyperpolarization of the diastolic membrane potential of ventricular myocytes. 2. The membrane potential (E(m)) of isolated rat myocytes was determined using the perforated patch-clamp technique and DiBac(4)(3) imaging. Intracellular Ca(2+) ([Ca(2+)](i)) was monitored using FURA-2 imaging. 3. CIH/reoxygenation caused a significant depolarization of E(m) and a substantial increase in [Ca(2+)](i). The K(ATP) opener pinacidil (100 microm) and the pmK(ATP) opener P-1075 (100 microm) hyperpolarized the E(m) of normoxic myocytes. Pinacidil (100 microm) and P-1075 (10 and 100 microm), applied during reoxygenation, hyperpolarized E(m) and prevented reoxygenation-induced increases in [Ca(2+)](i). 4. Myocyte hypercontracture and death increased in parallel with an E(m) depolarization of 10-15 mV and increases in [Ca(2+)](i). Under these conditions, the selective pmK(ATP) channel inhibitor HMR 1098 further depolarized myocyte membrane potential and increased hypercontracture. 5. In conclusion, activation of pmK(ATP) channels can prevent CIH/reoxygenation-induced Ca(2+) overload via a mechanism that is dependent on hyperpolarization of diastolic membrane potential. Hyperpolarization toward normal resting membrane potential favours the Ca(2+) extrusion mode of Na(+)/Ca(2+) exchange.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-10221990,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-10325234,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-10390518,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-10518593,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-10585102,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-10585103,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-10585111,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-10821820,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-11082408,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-11160857,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-11470463,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-11588107,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-11720973,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-11726534,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-11815384,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-11854323,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-11991732,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-6310409,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-7553711,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-8238595,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-8630239,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-9400389,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-9535004,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-9543494,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/14993099-9769309
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Barbiturates,
http://linkedlifedata.com/resource/pubmed/chemical/Benzamides,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescent Dyes,
http://linkedlifedata.com/resource/pubmed/chemical/G Protein-Coupled...,
http://linkedlifedata.com/resource/pubmed/chemical/HMR 1098,
http://linkedlifedata.com/resource/pubmed/chemical/Isoxazoles,
http://linkedlifedata.com/resource/pubmed/chemical/KCNJ5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Pinacidil,
http://linkedlifedata.com/resource/pubmed/chemical/Poloxamer,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels, Inwardly...,
http://linkedlifedata.com/resource/pubmed/chemical/Probenecid,
http://linkedlifedata.com/resource/pubmed/chemical/bis(1,3-dibutylbarbiturate)trimethin...
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0007-1188
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
141
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1059-67
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:14993099-Animals,
pubmed-meshheading:14993099-Calcium,
pubmed-meshheading:14993099-Rats,
pubmed-meshheading:14993099-Barbiturates,
pubmed-meshheading:14993099-Fluorescent Dyes,
pubmed-meshheading:14993099-Electric Stimulation,
pubmed-meshheading:14993099-Probenecid,
pubmed-meshheading:14993099-Benzamides,
pubmed-meshheading:14993099-Cell Membrane,
pubmed-meshheading:14993099-Membrane Potentials,
pubmed-meshheading:14993099-Patch-Clamp Techniques,
pubmed-meshheading:14993099-Cell Hypoxia,
pubmed-meshheading:14993099-Myocytes, Cardiac,
pubmed-meshheading:14993099-Isoxazoles,
pubmed-meshheading:14993099-Pinacidil,
pubmed-meshheading:14993099-Poloxamer,
pubmed-meshheading:14993099-Potassium Channels, Inwardly Rectifying
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