Plasma Membrane Ca2+ ATPase - Isoforms

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, calculated from its sequence. This is in good agreement with the results of SDS gel electrophoresis.