PMID- 24074949
OWN - NLM
STAT- MEDLINE
DCOM- 20140813
LR  - 20201209
IS  - 1096-0961 (Electronic)
IS  - 1079-9796 (Linking)
VI  - 52
IP  - 2-3
DP  - 2014 Feb-Mar
TI  - The canonical transient receptor potential 6 (TRPC6) channel is sensitive to 
      extracellular pH in mouse platelets.
PG  - 108-15
LID - S1079-9796(13)00204-0 [pii]
LID - 10.1016/j.bcmd.2013.08.007 [doi]
AB  - The canonical transient receptor potential-6 (TRPC6) is a receptor-activated 
      non-selective Ca(2+) channel regulated by a variety of modulators such as 
      diacylglycerol, Ca(2+)/calmodulin or phosphorylation. The present study is aimed 
      to investigate whether different situations, such as acidic pH, exposure to 
      reactive oxygen species (ROS) or hypoxic-like conditions modulate TRPC6 channel 
      function. Here we show normal aggregation and Ca(2+) mobilization stimulated by 
      thrombin in TRPC6 KO platelets; however, OAG 
      (1-oleoyl-2-acetyl-sn-glycerol)-evoked Ca(2+) entry was attenuated in the absence 
      of TRPC6. Exposure of mouse platelets to acidic pH resulted in abolishment of 
      thrombin-evoked aggregation and attenuated platelet aggregation induced by 
      thapsigargin (TG) or OAG. Both OAG-induced Ca(2+) entry and platelet aggregation 
      were greatly attenuated in cells expressing TRPC6 channels. Exposure of platelets 
      to H2O2 or deferoxamine did not clearly alter thrombin, TG or OAG-induced 
      platelet aggregation. Our results indicate that TRPC6 is sensitive to acidic pH 
      but not to exposure to ROS or hypoxic-like conditions, which might be involved in 
      the pathogenesis of the altered platelet responsiveness to DAG-generating 
      agonists in disorders associated to acidic pH.
CI  - (c) 2013.
FAU - Berna-Erro, Alejandro
AU  - Berna-Erro A
AD  - Department of Physiology (Cell Physiology Research Group), University of 
      Extremadura, 10003 Caceres, Spain.
FAU - Albarran, Letizia
AU  - Albarran L
AD  - Department of Physiology (Cell Physiology Research Group), University of 
      Extremadura, 10003 Caceres, Spain.
FAU - Dionisio, Natalia
AU  - Dionisio N
AD  - Department of Physiology (Cell Physiology Research Group), University of 
      Extremadura, 10003 Caceres, Spain.
FAU - Redondo, Pedro C
AU  - Redondo PC
AD  - Department of Physiology (Cell Physiology Research Group), University of 
      Extremadura, 10003 Caceres, Spain.
FAU - Alonso, Nieves
AU  - Alonso N
AD  - Department of Physiology (Cell Physiology Research Group), University of 
      Extremadura, 10003 Caceres, Spain.
FAU - Gomez, Luis J
AU  - Gomez LJ
AD  - Department of Physiology (Cell Physiology Research Group), University of 
      Extremadura, 10003 Caceres, Spain.
FAU - Salido, Gines M
AU  - Salido GM
AD  - Department of Physiology (Cell Physiology Research Group), University of 
      Extremadura, 10003 Caceres, Spain.
FAU - Rosado, Juan A
AU  - Rosado JA
AD  - Department of Physiology (Cell Physiology Research Group), University of 
      Extremadura, 10003 Caceres, Spain. Electronic address: jarosado@unex.es.
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130925
PL  - United States
TA  - Blood Cells Mol Dis
JT  - Blood cells, molecules & diseases
JID - 9509932
RN  - 0 (TRPC Cation Channels)
RN  - 0 (TRPC6 Cation Channel)
RN  - 0 (Trpc6 protein, mouse)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 3.4.21.5 (Thrombin)
RN  - J06Y7MXW4D (Deferoxamine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Blood Platelets/drug effects/*physiology
MH  - Calcium/metabolism
MH  - Deferoxamine/pharmacology
MH  - Extracellular Space/*metabolism
MH  - Hydrogen Peroxide/pharmacology
MH  - Hydrogen-Ion Concentration
MH  - Mice
MH  - Mice, Knockout
MH  - Platelet Aggregation/drug effects/genetics
MH  - TRPC Cation Channels/genetics/*metabolism
MH  - TRPC6 Cation Channel
MH  - Thrombin/pharmacology
OTO - NOTNLM
OT  - Aggregation
OT  - Calcium
OT  - Mouse platelets
OT  - OAG
OT  - TRPC6
OT  - pH
EDAT- 2013/10/01 06:00
MHDA- 2014/08/15 06:00
CRDT- 2013/10/01 06:00
PHST- 2013/07/25 00:00 [received]
PHST- 2013/08/20 00:00 [accepted]
PHST- 2013/10/01 06:00 [entrez]
PHST- 2013/10/01 06:00 [pubmed]
PHST- 2014/08/15 06:00 [medline]
AID - S1079-9796(13)00204-0 [pii]
AID - 10.1016/j.bcmd.2013.08.007 [doi]
PST - ppublish
SO  - Blood Cells Mol Dis. 2014 Feb-Mar;52(2-3):108-15. doi: 
      10.1016/j.bcmd.2013.08.007. Epub 2013 Sep 25.