Protein kinase C alpha enhances sodium–calcium exchange during store-operated calcium entry in mouse platelets

A rise in intracellular calcium concentration ([Ca2+]i) is necessary for platelet activation. A major component of the [Ca2+]i elevation occurs through store-operated Ca2+ entry (SOCE). The aim of this study was to understand the contribution of the classical PKC isoform, PKCα to platelet SOCE, using platelets from PKCα-deficient mice. SOCE was reduced by approximately 50% in PKCα−/− platelets, or following treatment with bisindolylmaleimide I, a PKC inhibitor. However, TG-induced Mn2+ entry was unaffected, which suggests that divalent cation entry through store-operated channels is not directly regulated. Blocking the autocrine action of secreted ADP or 5-HT on its receptors did not reproduce the effect of PKCα deficiency. In contrast, SN-6, a Na+/Ca2+ exchanger inhibitor, did reduce SOCE to the same extent as loss of PKCα, as did replacing extracellular Na+ with NMDG+. These treatments had no further effect in PKCα−/− platelets. These data suggest that PKCα enhances the extent of SOCE in mouse platelets by regulating Ca2+ entry through the Na+/Ca2+ exchanger.