Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 45, Pages 17867-17872Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0707722104
Keywords
atria; calcium uptake; sarcoplasmic reticulum Ca2+ ATPase 2
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Funding
- NHLBI NIH HHS [HL-64140, R01 HL064140, R01 HL068507, R01 HL075274] Funding Source: Medline
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Sarcolipin is a novel regulator of cardiac sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) and is expressed abundantly in atria. In this study we investigated the physiological significance of sarcolipin in the heart by generating a mouse model deficient for sarcolipin. The sarcolipin-null mice do not show any developmental abnormalities or any cardiac pathology. The absence of sarcolipin does not modify the expression level of other Ca2+ handling proteins, in particular phospholamban, and its phosphorylation status. Calcium uptake studies revealed that, in the atria, ablation of sarcolipin resulted in an increase in the affinity of the SERCA pump for Ca2+ and the maximum velocity of Ca2+ uptake rates. An important finding is that ablation of sarcolipin resulted in an increase in atrial Ca2+ transient amplitudes, and this resulted in enhanced atrial contractility. Furthermore, atria from sarcolipinnull mice showed a blunted response to isoproterenol stimulation, implicating sarcolipin as a mediator of A-adrenergic responses in atria. Our study documented that sarcolipin is a key regulator of SEIRCA2a in atria. Importantly, our data demonstrate the existence of distinct modulators for the SERCA pump in the atria and ventricles.
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