{{DISPLAYTITLE:Plasma membrane Ca2+ ATPase}} The plasma membrane Ca2+ ATPase (PMCA) is a transport protein in the plasma membrane of cells and functions to remove calcium (Ca2+) from the cell. PMCA function is vital for regulating the amount of Ca2+ within all eukaryotic cells. There is a very large transmembrane electrochemical gradient of Ca2+ driving the entry of the ion into cells, yet it is very important that they maintain low concentrations of Ca2+ for proper cell signalling. Thus, it is necessary for cells to employ ion pumps to remove the Ca2+. The PMCA and the sodium calcium exchanger (NCX) are together the main regulators of intracellular Ca2+ concentrations. Since it transports Ca2+ into the extracellular space, the PMCA is also an important regulator of the calcium concentration in the extracellular space. PMCAs belong to the family of P-type primary ion transport ATPases which form aspartyl phosphate intermediates. Various forms of PMCA are expressed in different tissues, including the brain. Actions The pump is powered by the hydrolysis of adenosine triphosphate (ATP), with a stoichiometry of one Ca2+ ion removed for each molecule of ATP hydrolysed. It binds tightly to Ca2+ ions (has a high affinity, with a Km of 100 to 200 nM) but does not remove Ca2+ at a very fast rate. This is in contrast to the NCX, which has a low affinity and a high capacity. Thus, the PMCA is effective at binding Ca2+ even when its concentrations within the cell are very low, so it is suited for maintaining Ca2+ at its normally very low levels. Calcium is an important second messenger, so its levels must be kept low in cells to prevent noise and keep signalling accurate. The NCX is better suited for removing large amounts of Ca2+ quickly, as is needed in neurons after an action potential. Thus the activities of the two types of pump complement each other. The PMCA functions in a similar manner to other p-type ion pumps. ATP transfers a phosphate to the PMCA, which forms a phosphorylated intermediate. Ca2+/calmodulin binds and further activates the PMCA, increasing the affinity of the protein's Ca2+-binding site 20 to 30 times. Calmodulin also increases the rate at which the pump extrudes Ca2+ from the cell, possibly up to tenfold. In brain tissue, it has been postulated that certain types of PMCA are important for regulating synaptic activity, since the PMCA is involved in