Ablation of sarcolipin enhances sarcoplasmic reticulum calcium transport and atrial contractility

Gopal J. Babu, Poornima Bhupathy, Valeriy Timofeyev, Natalia N. Petrashevskaya, Peter J. Reiser, Nipavan Chiamvimonvat, Muthu Periasamy

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Sarcolipin is a novel regulator of cardiac sarcoplasmic reticulum Ca 2+ 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 Ca 2+ 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 sarcolipin-null mice showed a blunted response to isoproterenol stimulation, implicating sarcolipin as a mediator of β-adrenergic responses in atria. Our study documented that sarcolipin is a key regulator of SERCA2a in atria. Importantly, our data demonstrate the existence of distinct modulators for the SERCA pump in the atria and ventricles.

Original languageEnglish (US)
Pages (from-to)17867-17872
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number45
DOIs
StatePublished - Nov 6 2007

Keywords

  • Atria
  • Calcium uptake
  • Sarcoplasmic reticulum Ca ATPase 2

ASJC Scopus subject areas

  • Genetics
  • General

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