Collaborative effect of SERCA and PMCA in cytosolic calcium homeostasis in human platelets

RESUMEN

Intracellular free Ca2+ concentration ([Ca2+]c) is finely regulated by several mechanismsthat either increase or reduce [Ca2+]c. Two different Ca2+ pumps have beendescribed so far as the main mechanisms for Ca2+ removal from the cytosol, either byits sequestration into the stores, mediated by the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) or by Ca2+ extrusion to the extracellular medium, by the plasmamembrane Ca2+-ATPase (PMCA). We have used inhibitors of these pumps to analyzetheir Ca2+ clearance efficacy in human platelets stimulated by the physiologicalagonist thrombin. Results demonstrate that, after platelet stimulation with thrombin,activation of SERCA precedes that of PMCA, although the ability of PMCA toremove Ca2+ from the cytosol last longer than that of SERCA. The efficacy ofSERCA and PMCA removing Ca2+ from the cytosol is reduced when the concentrationof thrombin increases. This phenomenon correlates with the greater increasein [Ca2+]c induced by higher concentrations of thrombin, which further confirmsthat SERCA and PMCA activities are regulated by [Ca2+]c