Plasma membrane Ca(2+)-pump functional specialization in the brain. Complex of isoform expression and regulation by effectors.

The plasma membrane Ca(2+)-pump (PMCA) is a key element in the removal of intracellular Ca2+. A number of PMCA pumps, encoded by a multigenic family and differing in their regulatory domains, also exist in the neuronal cells. We discuss here an idea regarding a new, higher level of specialization of PMCA protein isoforms with different sensitivities toward phospholipids and calmodulin. The idea is based on the kinetic data from PMCA stimulation by acidic phospholipids, with a combination of results describing an alternative RNA splicing at site A and C coding of regulatory domains of protein. The resulting complex modulation of the Ca(2+)-pump underlies the specific cellular requirements for Ca2+ homeostasis in a tissue-selective manner and is regulated by the level and spatial distribution of enzyme isoforms as well as by the level of their regulatory factors. The possible role of PMCA protein in the neuronal injury is also discussed.