The relative phospholamban and SERCA2 ratio: a critical determinant of myocardial contractility.
Basic Res Cardiol
; 92 Suppl 1: 17-24, 1997.
Article
em En
| MEDLINE
| ID: mdl-9202840
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Retículo Sarcoplasmático
/
Proteínas de Ligação ao Cálcio
/
ATPases Transportadoras de Cálcio
/
Contração Miocárdica
Limite:
Animals
Idioma:
En
Revista:
Basic Res Cardiol
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Estados Unidos