calculated from its sequence. This is in good agreement with the results of SDS gel electrophoresis. Pathology When the PMCA fails to function properly, disease can result. Improperly functioning PMCA proteins have been found associated with conditions such as sensorineural deafness, diabetes, and hypertension. In excitotoxicity, a process in which excessive amounts of the neurotransmitter glutamate overactivate neurons, resulting in excessive influx of Ca2+ into cells, the activity of the PMCA may be insufficient to remove the excess Ca2+. In breast tissue, mammary epithelial cells express PMCA2, which transports calcium across the apical surface of the cells into milk. PMCA2 expression falls on weaning, leading to calcium-induced apoptosis and mammary gland involution. Persistent PMCA2 expression in certain breast cancers lowers calcium levels inside malignant cells, allowing them to avoid apoptosis. These tumors are also usually positive for the HER2 protein, tend to involve the lymph nodes, and are more common among young women, which could help explain their worse prognosis compared with postmenopausal women. Curcumin can bind to the PMCA, inducing a conformational change that prevents ATP from binding. History PMCAs were first discovered in the 1960s in the membranes of red blood cells. The presence of an ATPase was discovered in the membranes in 1961, and then in 1966 it was discovered that these ATPases pump Ca2+ out of the cytosol. PMCA was first purified from red blood cell membranes in 1979. References External links Transmembrane transporters