Source:http://linkedlifedata.com/resource/pubmed/id/19683723
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2009-9-7
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| pubmed:abstractText |
Na,K-ATPase is composed of two essential alpha- and beta-subunits, both of which have multiple isoforms. Evidence indicates that the Na,K-ATPase enzymatic activity as well as its alpha(1), alpha(3) and beta(1) isoforms are reduced in the failing human heart. The catalytic alpha-subunit is the receptor for cardiac glycosides such as digitalis, used for the treatment of congestive heart failure. The role of the Na,K-ATPase beta(1)-subunit (Na,K-beta(1)) in cardiac function is not known. We used Cre/loxP technology to inactivate the Na,K-beta(1) gene exclusively in the ventricular cardiomyocytes. Animals with homozygous Na,K-beta(1) gene excision were born at the expected Mendelian ratio, grew into adulthood, and appeared to be healthy until 10 months of age. At 13-14 months, these mice had 13% higher heart/body weight ratios, and reduced contractility as revealed by echocardiography compared to their wild-type (WT) littermates. Pressure overload by transverse aortic constriction (TAC) in younger mice, resulted in compensated hypertrophy in WT mice, but decompensation in the Na,K-beta(1) KO mice. The young KO survivors of TAC exhibited decreased contractile function and mimicked the effects of the Na,K-beta(1) KO in older mice. Further, we show that intact hearts of Na,K-beta(1) KO anesthetized mice as well as isolated cardiomyocytes were insensitive to ouabain-induced positive inotropy. This insensitivity was associated with a reduction in NCX1, one of the proteins involved in regulating cardiac contractility. In conclusion, our results demonstrate that Na,K-beta(1) plays an essential role in regulating cardiac contractility and that its loss is associated with significant pathophysiology of the heart.
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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/Atp1b1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/NCX1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ouabain,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Calcium Exchanger,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Potassium-Exchanging ATPase
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
1095-8584
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| pubmed:author |
pubmed-author:BarweSonali PSP,
pubmed-author:DashBB,
pubmed-author:GoldhaberJoshua IJI,
pubmed-author:IngeLandonL,
pubmed-author:JohnsonChristina LCL,
pubmed-author:JordanMaria CMC,
pubmed-author:NecoPatriciaP,
pubmed-author:RajasekaranAyyappan KAK,
pubmed-author:RajasekaranSigrid ASA,
pubmed-author:RoosKenneth PKP,
pubmed-author:RozengurtNoraN,
pubmed-author:SkayAnnaA,
pubmed-author:WolleDanielD
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| pubmed:issnType |
Electronic
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| pubmed:volume |
47
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
552-60
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| pubmed:dateRevised |
2010-12-3
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| pubmed:meshHeading |
pubmed-meshheading:19683723-Aging,
pubmed-meshheading:19683723-Animals,
pubmed-meshheading:19683723-Calcium Signaling,
pubmed-meshheading:19683723-Cardiomegaly,
pubmed-meshheading:19683723-Cell Separation,
pubmed-meshheading:19683723-Gene Deletion,
pubmed-meshheading:19683723-Heart Function Tests,
pubmed-meshheading:19683723-Immunoblotting,
pubmed-meshheading:19683723-Mice,
pubmed-meshheading:19683723-Mice, Knockout,
pubmed-meshheading:19683723-Myocardial Contraction,
pubmed-meshheading:19683723-Myocardium,
pubmed-meshheading:19683723-Myocytes, Cardiac,
pubmed-meshheading:19683723-Organ Specificity,
pubmed-meshheading:19683723-Ouabain,
pubmed-meshheading:19683723-Pressure,
pubmed-meshheading:19683723-Protein Subunits,
pubmed-meshheading:19683723-Sodium-Calcium Exchanger,
pubmed-meshheading:19683723-Sodium-Potassium-Exchanging ATPase
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| pubmed:year |
2009
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| pubmed:articleTitle |
Dysfunction of ouabain-induced cardiac contractility in mice with heart-specific ablation of Na,K-ATPase beta1-subunit.
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| pubmed:affiliation |
Nemours Center for Childhood Cancer Research, Alfred I. duPont Hospital for Children, Rockland Center One, 1701 Rockland Road, Wilmington, DE 19803, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|