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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 (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 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 Related Letter in Blood Online Social Bookmarking                   What's this? Submitted March 7, 2002 Accepted May 22, 2002 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* CENTRE FOR CARDIOVASCULAR BIOLOGY AND MEDICINE, KING'S COLLEGE LONDON, LONDON, United Kingdom NEUROBIOTECHNOLOGY CENTRE, OHIO STATE UNIVERSITY, COLUMBUS, OHIO, USA INSTITUT FUR PHARMAKOLOGIE UND TOXIKOLOGIE, UNIVERSITAT DER SAARLANDES, HOMBURG, Germany * Corresponding author; email: kalwant.authi{at}kcl.ac.uk. Store operated Ca2+ entry (SOCE) is thought to comprise the major pathway for Ca2+ entry in platelets. Recently a number of transient receptor potential (TRP) proteins, that have been divided into three 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 (IM) membranes TRPC6 is found in the PM but TRPC1 is localised 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 Ca2+ and Ba2+ independent of protein kinase C. Thrombin also induced the entry of Ca2+ and Ba2+ but thapsigargin, which depletes the stores, only induced the entry of Ca2+. 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 Ca2+ but not Ba2+ entry, induced by thrombin and neither Ca2+ nor Ba2+ entry stimulated by OAG. These results suggest that TRPC6 is a SOCE independent, non-selective cation entry channel stimulated by thrombin and OAG. TRPC6 is a substrate for cAMP-PK although phosphorylation appears not to affect cation permeation. TRPC1 is located in IM suggesting a role at the level of the stores. 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. [Full Text] [PDF] This article has been cited by other articles: H. Matsuoka, K. Harada, T. Ikeda, K. Uetsuki, T. Sata, A. Warashina, and M. Inoue Ca2+ pathway involved in the refilling of store sites in rat adrenal medullary cells Am J Physiol Cell Physiol, April 1, 2009; 296(4): C889 - C899. [Abstract] [Full Text] [PDF] A. Braun, D. Varga-Szabo, C. Kleinschnitz, I. 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