Sarcoplasmic reticulum Ca^2+-ATPase (SERCA)

Sarcoplasmic reticulum Ca^2+-ATPase (SERCA) is an integral membrane enzyme of the P-type ATPase family; it actively transports calcium ions from the cytosol back into the sarcoplasmic reticulum in muscle cells, thereby enabling muscle relaxation and regulating cytosolic Ca^2+ concentration[1][3][5][6]. SERCA's activity is essential for normal cardiac and skeletal muscle contractility, with its function tightly controlled by regulatory proteins such as phospholamban and sarcolipin[4][5]. SERCA-mediated transport is achieved via ATP hydrolysis, with each catalytic cycle moving two Ca^2+ ions per ATP molecule into the SR lumen[2][3][4]. Pathological changes in SERCA activity or expression – due to oxidative stress, genetic mutation, or altered regulation – are implicated in heart failure, muscle diseases, and metabolic disorders, making SERCA a prominent drug target for therapeutic interventions aimed at restoring Ca^2+ homeostasis[1][2][5]. Inhibitors (e.g., thapsigargin, CPA) and experimental activators (e.g., istaroxime) modify SERCA function, with therapeutic potential and safety dependent upon specificity and modulation of Ca^2+ handling.

Other names

SERCACalcium pump ATPaseSR Ca^2+-ATPaseSarco(endo)plasmic reticulum Ca^2+-ATPaseCa^2+-pump ATPase

Inhibition: Prevents Ca^2+ re-entry into sarcoplasmic reticulum, prolonging cytosolic Ca^2+ elevation and suppressing contractility[3] Activation: Improves Ca^2+ uptake by sarcoplasmic reticulum, enhancing relaxation and contractile reserve[3] Uncoupling (by sarcolipin): Promotes ATP hydrolysis without Ca^2+ transport, increasing heat production[4]