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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2223-2228. Prepublished online as a Blood First Edition Paper on June 1, 2006; DOI 10.1182/blood-2006-01-009613. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-01-009613v1 108/7/2223    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wolfs, J. L. Articles by Bevers, E. M. Search for Related Content PubMed PubMed Citation Articles by Wolfs, J. L. Articles by Bevers, E. M. Related Collections Signal Transduction Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Reversible inhibition of the platelet procoagulant response through manipulation of the Gardos channel Jef L. Wolfs, Simone J. Wielders, Paul Comfurius, Theo Lindhout, John C. Giddings, Robert F. Zwaal, and Edouard M. Bevers From the Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands; and the Department of Haematology, Welsh National School of Medicine, Heath Park, Cardiff, United Kingdom. The platelet procoagulant response requires a sustained elevation of the intracellular Ca2+ concentration, [Ca2+]i, causing exposure of phosphatidylserine (PS) at the outer surface of the plasma membrane. An increased [Ca2+]i also activates Ca2+-dependent K+ channels. Here, we investigated the contribution of the efflux of K+ ions on the platelet procoagulant response in collagen-thrombin–activated platelets using selective K+ channel blockers. The Gardos channel blockers clotrimazol, charybdotoxin, and quinine caused a similar decrease in prothrombinase activity as well as in the number of PS-exposing platelets detected by fluorescence-conjugated annexin A5. Apamin and iberiotoxin, inhibitors of other K+ channels, were without effect. Only clotrimazol showed a significant inhibition of the collagen-plus-thrombin–induced intracellular calcium response. Clotrimazol and charybdotoxin did not inhibit aggregation and release under the conditions used. Inhibition by Gardos channel blockers was reversed by valinomycin, a selective K+ ionophore. The impaired procoagulant response of platelets from a patient with Scott syndrome was partially restored by pretreatment with valinomycin, suggesting a possible defect of the Gardos channel in this syndrome. Collectively, these results provide evidence for the involvement of efflux of K+ ions through Ca2+-activated K+ channels in the procoagulant response of platelets, opening potential strategies for therapeutic interventions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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