Document Detail

The relative phospholamban and SERCA2 ratio: a critical determinant of myocardial contractility.
MedLine Citation:
PMID:  9202840     Owner:  NLM     Status:  MEDLINE    
Phospholamban is a regulatory phosphoprotein which modulates the active transport of Ca2+ by the cardiac sarcoplasmic reticular Ca(2+)-ATPase enzyme (SERCA2) into the lumen of the sarcoplasmic reticulum. Phospholamban, which is a reversible inhibitor of SERCA2, represses the enzyme's activity, and this inhibition is relieved upon phosphorylation of phospholamban in response to beta-adrenergic stimulation. In this way, phospholamban is an important regulator of SERCA2-mediated myocardial relaxation during diastole. This report centers on the hypothesis that the relative levels of phospholamban: SERCA2 in cardiac muscle plays an important role in the muscle's overall contractility status. This hypothesis was tested by comparing the contractile parameters of: a) murine atrial and ventricular muscles, which differentially express phospholamban, and b) murine wild-type and phospholamban knock-out hearts. These comparisons revealed that atrial muscles, which have a 4.2-fold lower phospholamban: SERCA2 ratio than ventricular muscles, exhibited rates of force development and relaxation of tension, which were three-fold faster that these parameters for ventricular muscles. Similar comparisons were made via analyses of left-ventricular pressure development recorded for isolated, work-performing hearts from wild-type and phospholamban knock-out mice. In these studies, hearts from phospholamban knock-out mice, which were devoid of phospholamban, exhibited enhanced parameters of left-ventricular contractility in comparison to wild-type hearts. These results suggest that the relative phospholamban: SERCA2 ratio is critical in the regulation of myocardial contractility and alterations in this ratio may contribute to the functional deterioration observed during heart failure.
K L Koss; I L Grupp; E G Kranias
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Basic research in cardiology     Volume:  92 Suppl 1     ISSN:  0300-8428     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:  1997  
Date Detail:
Created Date:  1997-08-27     Completed Date:  1997-08-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  17-24     Citation Subset:  IM    
Dept. of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Ohio 45267-0575, USA.
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MeSH Terms
Animals, Wild
Calcium-Binding Proteins / genetics,  metabolism*
Calcium-Transporting ATPases / genetics,  metabolism*
Heart Atria
Heart Ventricles
Mice, Knockout / genetics
Myocardial Contraction / physiology*
Myocardium / enzymology
Sarcoplasmic Reticulum / enzymology*
Transcription, Genetic
Grant Support
Reg. No./Substance:
0/Calcium-Binding Proteins; 0/phospholamban; EC ATPases

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