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Prepublished online as a Blood First Edition Paper on June 21, 2002; DOI 10.1182/blood-2002-03-0723. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-03-0723v1 100/8/2801    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hassock, S. R. Articles by Authi, K. S. Search for Related Content PubMed PubMed Citation Articles by Hassock, S. R. Articles by Authi, K. S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 October 2002, Vol. 100, No. 8, pp. 2801-2811 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Expression and role of TRPC proteins in human platelets: evidence that TRPC6 forms the store-independent calcium entry channel Sheila R. Hassock, Michael X. Zhu, Claudia Trost, Veit Flockerzi, and Kalwant S. Authi From the Centre for Cardiovascular Biology and Medicine, King's College London, New Hunt's House, Guy's Campus, London; the Neurobiotechnology Centre, Ohio State University, Columbus; and the Institut für Pharmakologie und Toxikologie der Universität des Saarlandes, Homburg, Germany. Store-operated Ca++ entry (SOCE) is thought to comprise the major pathway for Ca++ entry in platelets. Recently, a number of transient receptor potential (TRP) proteins, which have been divided into 3 groups (TRPC, TRPM, and TRPV), have been suggested as SOCE channels. We report the expression and function of TRPC proteins in human platelets. TRPC6 is found at high levels and TRPC1 at low levels. Using purified plasma (PM) and intracellular membranes (IM), TRPC6 is found in the PM, but TRPC1 is localized to the IM. Using Fura-2-loaded platelets, we report that, in line with TRPC6 expression, 1-oleoyl-2-acetyl-sn-glycerol (OAG) stimulated the entry of Ca++ and Ba2+ independently of protein kinase C. Thrombin also induced the entry of Ca++ and Ba2+, but thapsigargin, which depletes the stores, induced the entry of only Ca++. Thus, thrombin activated TRPC6 via a SOCE-independent mechanism. In phosphorylation studies, we report that neither TRPC6 nor TRPC1 was a substrate for tyrosine kinases. TRPC6 was phosphorylated by cAMP-dependent protein kinase (cAMP-PK) and associated with other cAMP-PK substrates. TRPC1 was not phosphorylated by cAMP-PK but also associated with other substrates. Activation of cAMP-PK inhibited Ca++ but not Ba2+ entry induced by thrombin and neither Ca++ nor Ba2+ entry stimulated by OAG. These results suggest that TRPC6 is a SOCE-independent, nonselective cation entry channel stimulated by thrombin and OAG. TRPC6 is a substrate for cAMP-PK, although phosphorylation appears to not affect cation permeation. TRPC1 is located in IM, suggesting a role at the level of the stores. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: TRP channels and calcium entry in human platelets Stewart O. Sage, Sharon L. Brownlow, Juan A. Rosado, Kalwant S. Authi, Sheila Hassock, Michael X. Zhu, Veit Flockerzi, and Claudia Trost Blood 2002 100: 4245-4246. 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