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Publication : The canonical transient receptor potential 6 (TRPC6) channel is sensitive to extracellular pH in mouse platelets.

First Author  Berna-Erro A Year  2014
Journal  Blood Cells Mol Dis Volume  52
Issue  2-3 Pages  108-15
PubMed ID  24074949 Mgi Jnum  J:317966
Mgi Id  MGI:6840467 Doi  10.1016/j.bcmd.2013.08.007
Citation  Berna-Erro A, et al. (2014) The canonical transient receptor potential 6 (TRPC6) channel is sensitive to extracellular pH in mouse platelets. Blood Cells Mol Dis 52(2-3):108-15
abstractText  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.
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