title: Protein kinase C alpha enhances sodium-calcium exchange during store-operated calcium entry in mouse platelets.
abstract: A rise in intracellular calcium concentration ([Ca(2+)](i)) is necessary for platelet activation. A major component of the [Ca(2+)](i) elevation occurs through store-operated Ca(2+) 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 Mn(2+) 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(+)/Ca(2+) 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 Ca(2+) entry through the Na(+)/Ca(2+) exchanger.
authors.affiliation: School of Physiology and Pharmacology, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, United Kingdom.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Harper
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Molkentin
authors.forename: Alastair W
authors.initials: AW
authors.lastname: Poole
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D051379:Mice; D008822:Mice, Transgenic; D015539:Platelet Activation; D051571:Protein Kinase C-alpha / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000502:physiology*
chemical_list: D019831:Sodium-Calcium Exchanger; D000244:Adenosine Diphosphate; D012964:Sodium; D051571:Protein Kinase C-alpha; D002118:Calcium