Extracellular chloride is required for efficient activation of secondary signalling pathways during platelet aggregation

Taylor, Kirk A. and Wilson, Darren and Harper, Matthew T. and Pugh, Nicholas (2018) Extracellular chloride is required for efficient activation of secondary signalling pathways during platelet aggregation. Platelets, 29 (1). pp. 79-83. ISSN 1369-1635

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Official URL: http://dx.doi.org/10.1080/09537104.2017.1332367

Abstract

Anion channels perform a diverse range of functions and have been implicated in ATP release, volume regulation and phosphatidylserine exposure. Platelets have been shown to express several anion channels however their function is incompletely understood. Due to a paucity of specific pharmacological blockers, we investigated the global effect of extracellular chloride substitution on platelet activation using aggregometry and flow cytometry. In the absence of extracellular chloride we observed a modest effect on the maximum aggregation response to thrombin or collagen-related peptide. Although the rate of aggregation was substantially reduced in a manner that was dependent on the extracellular chloride concentration, aggregation in the absence of chloride was noticeably biphasic, indicative of impaired secondary signalling. This was further investigated by targeting secondary agonists with aspirin and apyrase or by blockade of the ADP receptor P2Y12. Under these conditions, the rates of aggregation were comparable to those recorded in the absence of extracellular chloride. Finally, we assessed platelet granule release by flow cytometry and report a chloride-dependent element of alpha, but not dense, granule secretion. Taken together these data support a role for anion channels in the efficient induction of platelet activation, likely via enhancement of secondary signalling pathways.

Item Type: Journal Article
Keywords: ADP, aggregation, chloride, ion channels platelets, thrombin
Faculty: Faculty of Science & Technology
Depositing User: Dr Nicholas Pugh
Date Deposited: 06 Jun 2017 10:20
Last Modified: 07 Jun 2019 15:34
URI: http://arro.anglia.ac.uk/id/eprint/701787

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