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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1996-10-22
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pubmed:abstractText |
In numerous studies the intracellular mononucleotide-dependent gating of ATP-sensitive K+ (KATP) channels has been demonstrated. However, it is not known whether dinucleotide polyphosphates, a family of endogenous compounds structurally-related to ATP, could also modulate this ion conductance. Therefore, in the present study we assessed the direct effect of diadenosine 5',5''-P1,P5-pentaphosphate (Ap5A) on cardiac KATP channel activity using the inside-out configuration of the patch-clamp technique. Addition of Ap5A (50 microM) to the internal side of membrane patches, excised from guinea-pig ventricular cells, strongly inhibited KATP channel activity. The estimated NPO (where N is the number of channels in the patch and PO the open probability of each channel) was 4.16 +/- 0.50 in the absence and 0.85 +/- 0.30 in the presence of Ap5A (50 microM). This effect of Ap5A was partially reversible, and the NP0 was 2.26 +/- 0.60 after washout of Ap5A. Exposure of KATP channels to increasing concentrations of Ap5A revealed that the Ap5A-induced inhibition is concentration-dependent with the half-maximal effective concentration of 16 microM (Hill coefficient: 1.6). On the basis of these results, we conclude that Ap5A is a potent antagonist of the KATP channel activity. This represents a previously unrecognized property of Ap5A, as well as the discovery of a potentially novel endogenous ligand of myocardial KATP channels.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Dinucleoside Phosphates,
http://linkedlifedata.com/resource/pubmed/chemical/P(1),P(5)-di(adenosine-5'-)pentaphos...,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Vasoconstrictor Agents
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0028-1298
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
353
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
241-4
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8717166-Adenosine Triphosphate,
pubmed-meshheading:8717166-Animals,
pubmed-meshheading:8717166-Dinucleoside Phosphates,
pubmed-meshheading:8717166-Dose-Response Relationship, Drug,
pubmed-meshheading:8717166-Guinea Pigs,
pubmed-meshheading:8717166-Heart,
pubmed-meshheading:8717166-Patch-Clamp Techniques,
pubmed-meshheading:8717166-Potassium Channels,
pubmed-meshheading:8717166-Vasoconstrictor Agents
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pubmed:year |
1996
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pubmed:articleTitle |
Cardiac ATP-sensitive K+ channel: a target for diadenosine 5',5''-P1,P5-pentaphosphate.
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pubmed:affiliation |
Division of Cardiovascular Diseases, Mayo Clinic, Mayo Foundation, Rochester, MN 55905, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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