Store-operated calcium entry and non-capacitative calcium entry have distinct roles in thrombin-induced calcium signalling in human platelets

Matthew T Harper, Alastair W Poole

Research output: Contribution to journalArticle (Academic Journal)

48 Citations (Scopus)

Abstract

Phosphatidylserine (PS)-exposing platelets accelerate coagulation at sites of vascular injury. PS exposure requires sustained Ca2+ signalling. Two distinct Ca2+ entry pathways amplify and sustain platelet Ca2+ signalling, but their relative importance in human platelets is not known. Here we examined the relative roles of store-operated Ca2+ entry (SOCE) and non-capacitative Ca2+ entry (NCCE) in thrombin-induced Ca2+ signalling and PS exposure by using two Ca2+ channel blockers. BTP-2 showed marked selectivity for SOCE over NCCE. LOE-908 specifically blocked NCCE under our conditions. Using these agents we found that SOCE is important at low thrombin concentrations whereas NCCE became increasingly important as thrombin concentration was increased. PS exposure was reduced by LOE-908, and only activated at thrombin concentrations that also activate NCCE. In contrast, BTP-2 had no effect on PS exposure. We suggest that SOCE amplifies and sustains Ca2+ signalling in response to low concentrations of thrombin whereas both NCCE and SOCE are important contributors to Ca2+ signalling at higher thrombin concentrations. However, despite being involved in Ca2+ signalling at high thrombin concentrations, SOCE is not important for thrombin-induced PS exposure in human platelets. This suggests that the route of Ca2+ entry is an important regulator of thrombin-induced PS exposure in platelets.
Original languageEnglish
Pages (from-to)351-8
Number of pages8
JournalCell Calcium
Volume50
Issue number4
DOIs
Publication statusPublished - Oct 2011

Bibliographical note

Copyright © 2011 Elsevier Ltd. All rights reserved.

Keywords

  • Thrombin
  • Isoquinolines
  • Anilides
  • Calcium
  • Spectrometry, Fluorescence
  • Dose-Response Relationship, Drug
  • Humans
  • Calcium Channel Blockers
  • Acetamides
  • Ion Transport
  • Phosphatidylserines
  • Calcium Channels
  • Blood Coagulation
  • Blood Platelets
  • Thiadiazoles
  • Fura-2
  • Calcium Signaling

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