Сақталмалы ретикулумның кальций АТФазасы және оның реттелуі

Calcium ATPase type P ATPase
SERCA, or sarcoplasmic/endoplasmic reticulum Ca2+ ATPase, or SR Ca2+ ATPase, is a calcium ATPase type P ATPase. Its major function is to transport calcium from the cytosol into the sarcoplasmic reticulum.

SERCA is a P type ATPase. It resides in the sarcoplasmic reticulum (SR) within myocytes. Along with the heat it naturally produces due to its inefficiency in pumping ions, when it binds to a regulator called sarcolipin it stops pumping and functions solely as an ATP hydrolase. This mechanism of thermogenesis is widespread in mammals and in endothermic fishes.

The rate at which SERCA moves Ca2+ across the SR membrane can be controlled by the regulatory protein phospholamban (PLB/PLN). SERCA is not as active when PLB is bound to it. Increased β adrenergic stimulation reduces the association between SERCA and PLB by the phosphorylation of PLB by PKA. When PLB is associated with SERCA, the rate of Ca2+ movement is reduced; upon dissociation of PLB, Ca2+ movement increases. Another protein, calsequestrin, binds calcium within the SR and helps to reduce the concentration of free calcium within the SR, which assists SERCA so that it does not have to pump against such a high concentration gradient. The SR has a much higher concentration of Ca2+ (10,000x) inside when compared to the cytoplasmic Ca2+ concentration. SERCA2 can be regulated by microRNAs, for instance miR 25 suppresses SERCA2 in heart failure. For experimental purposes, SERCA can be inhibited by thapsigargin and induced by istaroxime. SERCA function is upregulated in the skeletal muscle of rabbits and in rodent myocardium by thyroid hormones. This mechanism may contribute to the proarrhythmogenic effect of thyrotoxicosis.