Linked Life Data

15485817

Source:http://linkedlifedata.com/resource/pubmed/id/15485817

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
52
pubmed:dateCreated
2004-12-21
pubmed:abstractText
The primary objective of this study was to examine the functional role of the Na,K-ATPase alpha 1 isoform in the regulation of cardiac contractility. Previous studies using knock-out mice showed that the hearts of animals lacking one copy of the alpha 1 or alpha 2 isoform gene exhibit opposite phenotypes. Hearts from alpha 2(+/-) animals are hypercontractile, whereas those of the alpha 1(+/-) animals are hypocontractile. The cardiac phenotype of the alpha 1(+/-) animals was unexpected as other studies suggest that inhibition of either isoform increases contraction. To help resolve this difference, we have used genetically engineered knock-in mice expressing a ouabain-sensitive alpha 1 isoform and a ouabain-resistant alpha 2 isoform of the Na,K-ATPase, and we analyzed cardiac contractility following selective inhibition of the alpha1 isoform by ouabain. Administration of ouabain to these animals and to isolated heart preparations selectively inhibits only the activity of the alpha 1 isoform without affecting the activity of the alpha 2 isoform. Low concentrations of ouabain resulted in positive cardiac inotropy in both isolated hearts and intact animals expressing the modified alpha 1 and alpha 2 isoforms. Pretreatment with 10 microm KB-R7943, which inhibits the reverse mode of the Na/Ca exchanger, abolished the cardiotonic effects of ouabain in isolated wild type and knock-in hearts. Immunoprecipitation analysis demonstrated co-localization of the alpha1 isoform and the Na/Ca exchanger in cardiac sarcolemma. The alpha 1 isoform co-immunoprecipitated with the Na/Ca exchanger and vice versa. These results demonstrate that the alpha 1 isoform regulates cardiac contractility, and that both the alpha 1 and alpha 2 isoforms are functionally and physically coupled with the Na/Ca exchanger in heart.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
54053-61
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15485817-Animals, pubmed-meshheading:15485817-Base Sequence, pubmed-meshheading:15485817-Drug Resistance, pubmed-meshheading:15485817-Enzyme Inhibitors, pubmed-meshheading:15485817-Hemodynamics, pubmed-meshheading:15485817-Immunosorbent Techniques, pubmed-meshheading:15485817-Mice, pubmed-meshheading:15485817-Mice, Knockout, pubmed-meshheading:15485817-Molecular Sequence Data, pubmed-meshheading:15485817-Muscle, Skeletal, pubmed-meshheading:15485817-Mutagenesis, Site-Directed, pubmed-meshheading:15485817-Myocardial Contraction, pubmed-meshheading:15485817-Myocardium, pubmed-meshheading:15485817-Ouabain, pubmed-meshheading:15485817-Receptors, Adrenergic, beta, pubmed-meshheading:15485817-Sodium-Calcium Exchanger, pubmed-meshheading:15485817-Sodium-Potassium-Exchanging ATPase, pubmed-meshheading:15485817-Transfection, pubmed-meshheading:15485817-Tritium
pubmed:year
2004
pubmed:articleTitle
The alpha 1 isoform of Na,K-ATPase regulates cardiac contractility and functionally interacts and co-localizes with the Na/Ca exchanger in heart.
pubmed:affiliation
Department of Molecular Genetics, University of Cincinnati College of Medicine, Cincinanati, Ohio 45267, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.