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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1644-1651. Prepublished online as a Blood First Edition Paper on May 24, 2005; DOI 10.1182/blood-2005-02-0725. This Article Full Text (PDF) Supplemental Video All Versions of this Article: 2005-02-0725v1 106/5/1644    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 Tolhurst, G. Articles by Mahaut-Smith, M. P Search for Related Content PubMed PubMed Citation Articles by Tolhurst, G. Articles by Mahaut-Smith, M. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 23, 2005 Accepted May 8, 2005 Interplay between P2Y1, P2Y12 and P2X1 receptors in the activation of megakaryocyte cation influx currents by ADP; evidence that the primary megakaryocyte represents a fully functional model of platelet P2 receptor signaling Gwen Tolhurst, Catherine Vial, Catherine Leon, Christian Gachet, Richard J Evans, and Martyn P Mahaut-Smith* Department of Physiology, University of Cambridge, Cambridge, United Kingdom Department of Cell Physiology & Pharmacology, University of Leicester, Leicester, United Kingdom Institut National de la Sante et de la Recherche Medicale (INSERM) U.311, Strasbourg, France * Corresponding author; email: mpm11{at}cam.ac.uk. The difficulty of electrophysiological recordings from the platelet has restricted investigations into the role of ion channels in thrombosis and haemostasis. We now demonstrate that the well-established synergy between P2Y1 and P2Y12 receptors during ADP-dependent activation of the platelet IIb3 integrin also exists in murine marrow megakaryocytes, further supporting the progenitor cell as a bonafide model of platelet P2 receptor signalling. In patch clamp recordings, ADP (30 µM) stimulated a transient inward current at -70 mV, which was carried by Na+ and Ca2+ and amplified by phenylarsine oxide, a potentiator of certain TRP channels via phosphatidylinositol 4,5-bisphosphate depletion. This initial current decayed to a sustained phase, upon which were superimposed repetitive transient inward cation currents with predominantly P2X1-like kinetics. Abolishing P2X1 receptor activity prevented most of the repetitive currents, consistent with their activation by secreted ATP. Recordings in P2Y1 receptor-deficient megakaryocytes demonstrated an essential requirement of this receptor for activation of all ADP-evoked inward currents. However, P2Y12 receptors, via activation of PI-3 kinase, played a synergistic role in both P2Y1 and P2X1 receptor-dependent currents. Thus, direct stimulation of P2Y1 and P2Y12 receptors, together with autocrine P2X1 activation, are responsible for activation of non-selective cation currents by the platelet agonist ADP. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. Kumar, R. Fricke, D. Bhar, S. Reddy-Alla, K. S. Krishnan, S. Bogdan, and M. Ramaswami Syndapin Promotes Formation of a Postsynaptic Membrane System in Drosophila Mol. Biol. Cell, April 15, 2009; 20(8): 2254 - 2264. [Abstract] [Full Text] [PDF] R. N. Carter, G. Tolhurst, G. Walmsley, M. Vizuete-Forster, N. Miller, and M. P. Mahaut-Smith Molecular and electrophysiological characterization of transient receptor potential ion channels in the primary murine megakaryocyte J. Physiol., October 1, 2006; 576(1): 151 - 162. [Abstract] [Full Text] [PDF]

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