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

School of Physiology and Pharmacology, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, United Kingdom.
Cell calcium (Impact Factor: 3.51). 12/2010; 48(6):333-40. DOI: 10.1016/j.ceca.2010.10.006
Source: PubMed


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.

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    • "The role of individual isoforms in platelet activation has been investigated using isoform-specific inhibitors and mice deficient in single isoforms [4–7,9–19]. This has led to the conclusion that the classical isoforms play positive roles in platelet activation, with PKCα playing the predominant role, supported by PKCβ, while the novel isoforms play minor or inhibitory roles [10]. "
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