The Plasma Membrane Ca²⁺ ATPase and the Plasma Membrane Sodium Calcium Exchanger Cooperate in the Regulation of Cell Calcium

Abstract

Calcium is an ambivalent signal: it is essential for the correct functioning of cell life, but may also become dangerous to it. The plasma membrane Ca²⁺ ATPase (PMCA) and the plasma membrane Na⁺/Ca²⁺ exchanger (NCX) are the two mechanisms responsible for Ca²⁺ extrusion. The NCX has low Ca²⁺ affinity but high capacity for Ca²⁺ transport, whereas the PMCA has a high Ca²⁺ affinity but low transport capacity for it. Thus, traditionally, the PMCA pump has been attributed a housekeeping role in maintaining cytosolic Ca²⁺, and the NCX the dynamic role of counteracting large cytosolic Ca²⁺ variations (especially in excitable cells). This view of the roles of the two Ca²⁺ extrusion systems has been recently revised, as the specific functional properties of the numerous PMCA isoforms and splicing variants suggests that they may have evolved to cover both the basal Ca²⁺ regulation (in the 100 nM range) and the Ca²⁺ transients generated by cell stimulation (in the μM range).