Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-7-20
pubmed:abstractText
Ectopic expression of the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) 1a pump in the mouse heart results in a 2.5-fold increase in total SERCA pump level. SERCA1a hearts show increased rates of contraction/relaxation and enhanced Ca(2+) transients; however, the cellular mechanisms underlying altered Ca(2+) handling in SERCA1a transgenic (TG) hearts are unknown. In this study, using confocal microscopy, we demonstrate that SERCA1a protein traffics to the cardiac SR and structurally substitutes for the endogenous SERCA2a isoform. SR Ca(2+) load measurements revealed that TG myocytes have significantly enhanced SR Ca(2+) load. Confocal line-scan images of field-stimulated SR Ca(2+) release showed an increased rate of Ca(2+) removal in TG myocytes. On the other hand, ryanodine receptor binding activity was decreased by approximately 30%. However, TG myocytes had a greater rate of spontaneous ryanodine receptor opening as measured by spark frequency. Whole-cell L-type Ca(2+) current density was reduced by approximately 50%, whereas the time course of inactivation was unchanged in TG myocytes. These studies provide important evidence that SERCA1a can substitute both structurally and functionally for SERCA2a in the heart and that SERCA1a overexpression can be used to enhance SR Ca(2+) transport and cardiac contractility.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
20
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
160-7
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:11463723-Animals, pubmed-meshheading:11463723-Binding, Competitive, pubmed-meshheading:11463723-Blotting, Western, pubmed-meshheading:11463723-Caffeine, pubmed-meshheading:11463723-Calcium, pubmed-meshheading:11463723-Calcium Channels, L-Type, pubmed-meshheading:11463723-Calcium-Transporting ATPases, pubmed-meshheading:11463723-Heart, pubmed-meshheading:11463723-Homeodomain Proteins, pubmed-meshheading:11463723-Membrane Potentials, pubmed-meshheading:11463723-Mice, pubmed-meshheading:11463723-Mice, Transgenic, pubmed-meshheading:11463723-Myocardial Contraction, pubmed-meshheading:11463723-Myocardium, pubmed-meshheading:11463723-RNA, Messenger, pubmed-meshheading:11463723-Ryanodine, pubmed-meshheading:11463723-Ryanodine Receptor Calcium Release Channel, pubmed-meshheading:11463723-Sarcoplasmic Reticulum
pubmed:year
2001
pubmed:articleTitle
Sarcoplasmic reticulum Ca(2+) atpase (SERCA) 1a structurally substitutes for SERCA2a in the cardiac sarcoplasmic reticulum and increases cardiac Ca(2+) handling capacity.
pubmed:affiliation
Division of Cardiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.