regulating the amount of calcium within the cell at the synapse, and Ca2+ is involved in release of synaptic vesicles. Additionally, it has been shown that PMCA activity is modulated and partly powered by glycolysis in neuronal somata and dendrites. Presumably, it is due to PMCA proximity to glucose transporters in the plasma membrane. Structure The structure of the PMCA is similar to that of the SERCA calcium pumps, which are responsible for removing calcium from the cytoplasm into the lumen of the sarcoplasmic reticulum. Calcium tends to have a slightly lower affinity for PMCA pumps than for SERCA pumps. It is thought that the PMCA pump has 10 segments that cross the plasma membrane, with both C and N termini on the inside of the cell. At the C terminus, there is a long "tail" of between 70 and 200 amino acids in length. This tail is thought to be responsible for regulation of the pump. PMCA pumps have a molecular mass of around 140 kDa. Isoforms There are four isoforms of PMCA, called PMCA 1 through 4. ATP2B1 - PMCA1 ATP2B2 - PMCA2 ATP2B3 - PMCA3 ATP2B4 - PMCA4 Each isoform is coded by a different gene and is expressed in different areas of the body. Alternate splicing of the mRNA transcripts of these genes results in different subtypes of these isoforms. Over 20 splice variants have been identified so far. Three PMCA isoforms, PMCA1, PMCA2, and PMCA3, occur in the brain in varying distributions. PMCA1 is ubiquitous throughout all tissues in humans, and without it embryos do not survive. Lack of PMCA4, which is also very common in many tissues, is survivable, but leads to infertility in males. PMCA types 2 and 3 are activated more quickly and are, therefore, better suited to excitable cell types such as those in nervous and muscle tissue, which experiences large influxes of Ca2+ when excited. PMCA types 1, 2, and 4 have been found in glial cells called astrocytes in mammals, though it was previously thought that only the NCX was present in glia. Astrocytes help to maintain ionic balance in the extracellular space in the brain. Knock-out of PMCA2 causes inner ear problems, including hearing loss and problems with balance. PMCA4 exists in caveolae. Isoform PMCA4b interacts with nitric oxide synthase and reduces synthesis of nitric oxide by that enzyme. PMCA isoform 4 has a molecular weight of 134,683,