rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2003-9-3
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pubmed:abstractText |
The thin filament protein cardiac troponin T (cTnT) is an important regulator of myofilament activation. Here we report a significant change in cardiac energetics in transgenic mice bearing the missense mutation R92Q within the tropomyosin-binding domain of cTnT, a mutation associated with a clinically severe form of familial hypertrophic cardiomyopathy. This functional domain of cTnT has recently been shown to be a crucial modulator of contractile function despite the fact that it does not directly interact with the ATP hydrolysis site in the myosin head. Simultaneous measurements of cardiac energetics using 31P NMR spectroscopy and contractile performance of the intact beating heart revealed both a decrease in the free energy of ATP hydrolysis available to support contractile work and a marked inability to increase contractile performance upon acute inotropic challenge in hearts from R92Q mice. These results show that alterations in thin filament protein structure and function can lead to significant defects in myocardial energetics and contractile reserve.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12952925-10449439,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12952925-10980884,
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9738
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
112
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
768-75
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:12952925-Adenosine Triphosphate,
pubmed-meshheading:12952925-Animals,
pubmed-meshheading:12952925-Cardiomyopathy, Hypertrophic,
pubmed-meshheading:12952925-Disease Models, Animal,
pubmed-meshheading:12952925-Energy Metabolism,
pubmed-meshheading:12952925-Humans,
pubmed-meshheading:12952925-Mice,
pubmed-meshheading:12952925-Mutation,
pubmed-meshheading:12952925-Myocardial Contraction,
pubmed-meshheading:12952925-Myocardium,
pubmed-meshheading:12952925-Troponin T
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pubmed:year |
2003
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pubmed:articleTitle |
Decreased energetics in murine hearts bearing the R92Q mutation in cardiac troponin T.
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pubmed:affiliation |
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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