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Expression profiling and electrophysiological studies suggest a major role for Orai1 in the store-operated Ca2+ influx pathway of platelets and megakaryocytes

Tolhurst, Gwen; Carter, Richard N; Amisten, Stefan LU ; Holdich, Jon P.; Erlinge, David LU and Mahaut-Smith, Martyn P (2008) In Platelets 19(4). p.308-313
Abstract
Store-operated Ca2+ influx represents a major route by which cytosolic Ca2+ can be elevated during platelet activation, yet its molecular identity in this cell type remains highly controversial. Using quantitative RT-PCR analysis of candidate receptor-operated cation entry pathways in human platelets, we show a 30-fold higher expression of message for the recently discovered Orai1 store-operated Ca2+ channel, and also the store Ca2+ sensor STIM1, when compared to the non-selective cation channels TRPC1, TRPC6 and TRPM2. Orai1 and STIM1 gene transcripts were also detected at higher levels than TRPC1, TRPC6 and TRPM2 in primary murine megakaryocytes and human megakaryocytic cell lines. In direct electrophysiological recordings from murine... (More)
Store-operated Ca2+ influx represents a major route by which cytosolic Ca2+ can be elevated during platelet activation, yet its molecular identity in this cell type remains highly controversial. Using quantitative RT-PCR analysis of candidate receptor-operated cation entry pathways in human platelets, we show a 30-fold higher expression of message for the recently discovered Orai1 store-operated Ca2+ channel, and also the store Ca2+ sensor STIM1, when compared to the non-selective cation channels TRPC1, TRPC6 and TRPM2. Orai1 and STIM1 gene transcripts were also detected at higher levels than TRPC1, TRPC6 and TRPM2 in primary murine megakaryocytes and human megakaryocytic cell lines. In direct electrophysiological recordings from murine megakaryocytes, Ca2+ ionophore-induced store depletion stimulated CRAC currents, which are known to require Orai1, and these overlapped with TRPC6-like currents following P2Y receptor activation. Together with recent transgenic studies, these data provide evidence for STIM1:Orai1 as a primary pathway for agonist-evoked Ca2+ influx in the platelet and megakaryocyte. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
store-operated, megakaryocyte, STIM1, CRAC, Orai1, platelets, calcium, Ca2+ entry
in
Platelets
volume
19
issue
4
pages
308 - 313
publisher
Taylor & Francis
external identifiers
  • wos:000257069000009
  • scopus:45749095825
ISSN
1369-1635
DOI
10.1080/09537100801935710
language
English
LU publication?
yes
id
053f19d6-d2c1-45be-a07f-a79cd747bed4 (old id 1186346)
date added to LUP
2008-09-03 14:48:45
date last changed
2017-08-06 03:58:52
@article{053f19d6-d2c1-45be-a07f-a79cd747bed4,
  abstract     = {Store-operated Ca2+ influx represents a major route by which cytosolic Ca2+ can be elevated during platelet activation, yet its molecular identity in this cell type remains highly controversial. Using quantitative RT-PCR analysis of candidate receptor-operated cation entry pathways in human platelets, we show a 30-fold higher expression of message for the recently discovered Orai1 store-operated Ca2+ channel, and also the store Ca2+ sensor STIM1, when compared to the non-selective cation channels TRPC1, TRPC6 and TRPM2. Orai1 and STIM1 gene transcripts were also detected at higher levels than TRPC1, TRPC6 and TRPM2 in primary murine megakaryocytes and human megakaryocytic cell lines. In direct electrophysiological recordings from murine megakaryocytes, Ca2+ ionophore-induced store depletion stimulated CRAC currents, which are known to require Orai1, and these overlapped with TRPC6-like currents following P2Y receptor activation. Together with recent transgenic studies, these data provide evidence for STIM1:Orai1 as a primary pathway for agonist-evoked Ca2+ influx in the platelet and megakaryocyte.},
  author       = {Tolhurst, Gwen and Carter, Richard N and Amisten, Stefan and Holdich, Jon P. and Erlinge, David and Mahaut-Smith, Martyn P},
  issn         = {1369-1635},
  keyword      = {store-operated,megakaryocyte,STIM1,CRAC,Orai1,platelets,calcium,Ca2+ entry},
  language     = {eng},
  number       = {4},
  pages        = {308--313},
  publisher    = {Taylor & Francis},
  series       = {Platelets},
  title        = {Expression profiling and electrophysiological studies suggest a major role for Orai1 in the store-operated Ca2+ influx pathway of platelets and megakaryocytes},
  url          = {http://dx.doi.org/10.1080/09537100801935710},
  volume       = {19},
  year         = {2008},
}