The phosphatase activity of the plasma membrane Ca2+ pump. Activation by acidic lipids in the absence of Ca2+ increases the apparent affinity for Mg2+

Abstract

The purified PMCA supplemented with phosphatidylcholine was able to hydrolyze pNPP in a reaction media containing only Mg(2+) and K(+). Micromolar concentrations of Ca(2+) inhibited about 75% of the pNPPase activity while the inhibition of the remainder 25% required higher Ca(2+) concentrations. Acidic lipids increased 5-10 fold the pNPPase activity either in the presence or in the absence of Ca(2+). The activation by acidic lipids took place without a significant change in the apparent affinities for pNPP or K(+) but the apparent affinity of the enzyme for Mg(2+) increased about 10 fold. Thus, the stimulation of the pNPPase activity of the PMCA by acidic lipids was maximal at low concentrations of Mg(2+). Although with differing apparent affinities vanadate, phosphate, ATP and ADP were all inhibitors of the pNPPase activity and their effects were not significantly affected by acidic lipids. These results indicate that (a) the phosphatase function of the PMCA is optimal when the enzyme is in its activated Ca(2+) free conformation (E2) and (b) the PMCA can be activated by acidic lipids in the absence of Ca(2+) and the activation improves the interaction of the enzyme with Mg(2+).

Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels

“…This gene encodes plasma-membrane calcium ATPase 1 (PMCA1) [22], responsible for the removal of calcium ions from cells. One previous study reported that the phosphatase activity of PMCA1 is dependent on magnesium ions [23]. While magnesium uptake via TRPM6 at the apical membrane of epithelial cells has been demonstrated as the mechanism for magnesium entry, the mechanism by which magnesium ions exit the cells at the basolateral membrane is hitherto unknown [9].…”

Role of Ca2+ entry and Ca2+ stores in atypical smooth muscle cell autorhythmicity in the mouse renal pelvis

“…This difference may well arise from changes in the function of the plasma membrane Ca 2+ ATPase (PMCA) in the presence of Ca 2+ free PSS versus CPA. It has recently been demonstrated that the phosphatase activity of red blood cell PMCA is maximal in the absence of Ca 2+ and this activity is highly dependent on the Mg 2+ concentration (Mazzitelli and Adamo, 2007). A similar modulation of PMCA Ca 2+ extrusion in our Ca 2+ free PSS which contains a raised Mg 2+ concentration (3.5 m M ) could well be responsible for the fall in basal [Ca 2+ ] i occurring in our experiments.…”

Distal Convoluted Tubule

“…A recent association study found that variants in the PMCA1 gene are associated with serum Mg 2+ concentrations (337). One previous study reported that the phosphatase activity of PMCA1 is dependent on magnesium ions (323), suggesting it might fulfill the role of a basolateral Mg 2+ pump.…”