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Title: New perspectives on the role of SERCA2's Ca(2+) affinity in cardiac function
Authors: Vangheluwe, Peter ×
Sipido, Karin
Raeymaekers, Luc
Wuytack, Frank #
Issue Date: Nov-2006
Publisher: Elsevier
Series Title: Biochimica et Biophysica Acta. Molecular Cell Research vol:1763 issue:11 pages:1216-1228
Abstract: Cardiomyocyte relaxation and contraction are tightly controlled by the activity of the cardiac sarco(endo)plasmic reticulum (SR) Ca(2+) transport ATPase (SERCA2a). The SR Ca(2+)-uptake activity not only determines the speed of Ca(2+) removal during relaxation, but also the SR Ca(2+) content and therefore the amount of Ca(2+) released for cardiomyocyte contraction. The Ca(2+) affinity is the major determinant of the pump's activity in the physiological Ca(2+) concentration range. In the heart, the affinity of the pump for Ca(2+) needs to be controlled between narrow borders, since an imbalanced affinity may evoke hypertrophic cardiomyopathy. Several small proteins (phospholamban, sarcolipin) adjust the Ca(2+) affinity of the pump to the physiological needs of the cardiomyocyte. It is generally accepted that a chronically reduced Ca(2+) affinity of the pump contributes to depressed SR Ca(2+) handling in heart failure. Moreover, a persistently lower Ca(2+) affinity is sufficient to impair cardiomyocyte SR Ca(2+) handling and contractility inducing dilated cardiomyopathy in mice and humans. Conversely, the expression of SERCA2a, a pump with a lower Ca(2+) affinity than the housekeeping isoform SERCA2b, is crucial to maintain normal cardiac function and growth. Novel findings demonstrated that a chronically increased Ca(2+) affinity also may trigger cardiac hypertrophy in mice and humans. In addition, recent studies suggest that some models of heart failure are marked by a higher affinity of the pump for Ca(2+), and hence by improved cardiomyocyte relaxation and contraction. Depressed cardiomyocyte SR Ca(2+) uptake activity may therefore not be a universal hallmark of heart failure.
URI: 
ISSN: 0167-4889
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Physiology Section (-)
Cardiology
Experimental Cardiology
Laboratory of Cellular Transport Systems
× corresponding author
# (joint) last author

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