Ablation of phospholamban and sarcolipin results in cardiac hypertrophy and decreased cardiac contractility

Mayilvahanan Shanmugam, Shumin Gao, Chull Hong, Nadezhda Fefelova, Martha C. Nowycky, Lai Hua Xie, Muthu Periasamy, Gopal J. Babu

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


AimsImproving the sarco(endo)plasmic reticulum (SR) Ca2-ATPase (SERCA) function has clinical implications in treating heart failure. The present study aimed to determine the effect of constitutive activation of the SERCA pump on cardiac contractility in normal mice and during pressure-overload-induced cardiac hypertrophy. Methods and resultsThe SERCA pump was constitutively activated in both atrial and ventricular chambers of the mouse heart by ablating its key regulators, phospholamban (PLN) and sarcolipin (SLN). The double-knockout (dKO) mice for PLN and SLN showed increased SERCA pump activity, Ca2 transients and SR Ca2 load, and developed cardiac hypertrophy. Echocardiographic measurements showed that the basal cardiac function was not affected in the young dKO mice. However, the cardiac function worsened upon ageing and when subjected to pressure overload. ConclusionOur studies suggest that the constitutive activation of the SERCA pump is detrimental to cardiac function. Our findings also emphasize the need for dynamic regulation of the SERCA pump by PLN and/or SLN to maintain cardiac contractility in normal conditions and during pathophysiological states.

Original languageEnglish (US)
Pages (from-to)353-361
Number of pages9
JournalCardiovascular research
Issue number2
StatePublished - Feb 1 2011

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


  • Aortic banding
  • Calcium
  • Calcium transient
  • Cardiac function
  • Double knockout
  • Phospholamban
  • Sarcolipin


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