PMID- 17383000
OWN - NLM
STAT- MEDLINE
DCOM- 20080226
LR  - 20161124
IS  - 0143-4160 (Print)
IS  - 0143-4160 (Linking)
VI  - 42
IP  - 6
DP  - 2007 Dec
TI  - A key role for reverse Na+/Ca2+ exchange influenced by the actin cytoskeleton in 
      store-operated Ca2+ entry in human platelets: evidence against the de novo 
      conformational coupling hypothesis.
PG  - 606-17
AB  - We have previously demonstrated a role for the reorganization of the actin 
      cytoskeleton in store-operated calcium entry (SOCE) in human platelets and 
      interpreted this as evidence for a de novo conformational coupling step in SOCE 
      activation involving the type II IP(3) receptor and the platelet 
      hTRPC1-containing store-operated channel (SOC). Here, we present evidence 
      challenging this model. The actin polymerization inhibitors cytochalasin D or 
      latrunculin A significantly reduced Ca2+ but not Mn2+ or Na+ entry into 
      thapsigargin (TG)-treated platelets. Jasplakinolide, which induces actin 
      polymerization, also inhibited Ca2+ but not Mn2+ or Na+ entry. However, an 
      anti-hTRPC1 antibody inhibited TG-evoked entry of all three cations, indicating 
      that they all permeate an hTRPC1-containing store-operated channel (SOC). These 
      results indicate that the reorganization of the actin cytoskeleton is not 
      involved in SOC activation. The inhibitors of the Na+/Ca2+ exchanger (NCX), 
      KB-R7943 or SN-6, caused a dose-dependent inhibition of Ca2+ but not Mn2+ or Na+ 
      entry into TG-treated platelets. The effects of the NCX inhibitors were not 
      additive with those of actin polymerization inhibitors, suggesting a common point 
      of action. These results indicate a role for two Ca2+ permeable pathways 
      activated following Ca2+ store depletion in human platelets: A Ca2+-permeable, 
      hTRPC1-containing SOC and reverse Na+/Ca2+ exchange, which is activated following 
      Na+ entry through the SOC and requires a functional actin cytoskeleton.
FAU - Harper, Alan G S
AU  - Harper AG
AD  - Department of Physiology, Development and Neuroscience, University of Cambridge, 
      Cambridge CB2 3EG, UK.
FAU - Sage, Stewart O
AU  - Sage SO
LA  - eng
GR  - 064070/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070323
PL  - Netherlands
TA  - Cell Calcium
JT  - Cell calcium
JID - 8006226
RN  - 0 (2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate)
RN  - 0 (2-(4-(4-nitrobenzyloxy)benzyl)thiazolidine-4-carboxylic acid ethyl ester)
RN  - 0 (Actins)
RN  - 0 (Benzyl Compounds)
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Depsipeptides)
RN  - 0 (Sodium-Calcium Exchanger)
RN  - 0 (Thiazolidines)
RN  - 102396-24-7 (jasplakinolide)
RN  - 22144-77-0 (Cytochalasin D)
RN  - 42Z2K6ZL8P (Manganese)
RN  - 67526-95-8 (Thapsigargin)
RN  - 9NEZ333N27 (Sodium)
RN  - GYV9AM2QAG (Thiourea)
RN  - RWP5GA015D (Potassium)
RN  - SRQ9WWM084 (latrunculin A)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Actins/*metabolism
MH  - Benzyl Compounds/pharmacology
MH  - Blood Platelets/drug effects/*metabolism
MH  - Bridged Bicyclo Compounds, Heterocyclic/pharmacology
MH  - Calcium/*metabolism/pharmacology
MH  - Cytochalasin D/pharmacology
MH  - Cytoskeleton/*metabolism
MH  - Depsipeptides/pharmacology
MH  - Humans
MH  - Manganese/metabolism
MH  - Potassium/metabolism/pharmacology
MH  - Sodium/metabolism/pharmacology
MH  - Sodium-Calcium Exchanger/antagonists & inhibitors/*physiology
MH  - Thapsigargin/pharmacology
MH  - Thiazolidines/pharmacology
MH  - Thiourea/analogs & derivatives/pharmacology
EDAT- 2007/03/27 09:00
MHDA- 2008/02/27 09:00
CRDT- 2007/03/27 09:00
PHST- 2006/10/13 00:00 [received]
PHST- 2007/02/13 00:00 [revised]
PHST- 2007/02/13 00:00 [accepted]
PHST- 2007/03/27 09:00 [pubmed]
PHST- 2008/02/27 09:00 [medline]
PHST- 2007/03/27 09:00 [entrez]
AID - S0143-4160(07)00041-3 [pii]
AID - 10.1016/j.ceca.2007.02.004 [doi]
PST - ppublish
SO  - Cell Calcium. 2007 Dec;42(6):606-17. doi: 10.1016/j.ceca.2007.02.004. Epub 2007 
      Mar 23.