Sarco(endo)plasmic Reticulum Ca²⁺ ATPase Isoforms and Their Role in Muscle Physiology and Pathology

Abstract

Recent studies suggest that SR Ca2+ transport function is altered in hypertrophied and failing myocardium. To understand whether alterations in SR Ca2+ ATPase levels affect myocardial contractility, we generated transgenic mice that specifically overexpress SERCA2a or SERCA1 pump in the mouse heart, using the cardiac alpha-MHC promoter. Analysis of SERCA2a transgenic mice show both an increase in mRNA and protein levels (120-150% of the wild type). Isolated work performing heart preparations revealed that SERCA2a mice have improved myocardial performance. On the other hand, SERCA1 overexpression in the heart resulted in isoform replacement without any change in total SERCA protein. Interestingly, SERCA1 transgenic hearts exhibited super contractility with a significant increase in rates of muscle contraction (+dp/dt) and relaxation (-dp/dT). The time to peak pressure and half-time to relaxation were significantly shorter.