The canonical transient receptor potential 6 (TRPC6) channel is sensitive to extracellular pH in mouse platelets.
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.
Department of Physiology (Cell Physiology Research Group), University of Extremadura, 10003 Cáceres, Spain.
Alejandro
A
Berna-Erro
Department of Physiology (Cell Physiology Research Group), University of Extremadura, 10003 Cáceres, Spain.
Letizia
L
Albarran
Department of Physiology (Cell Physiology Research Group), University of Extremadura, 10003 Cáceres, Spain.
Natalia
N
Dionisio
Department of Physiology (Cell Physiology Research Group), University of Extremadura, 10003 Cáceres, Spain.
Pedro C
PC
Redondo
Department of Physiology (Cell Physiology Research Group), University of Extremadura, 10003 Cáceres, Spain.
Nieves
N
Alonso
Department of Physiology (Cell Physiology Research Group), University of Extremadura, 10003 Cáceres, Spain.
Luis J
LJ
Gomez
Department of Physiology (Cell Physiology Research Group), University of Extremadura, 10003 Cáceres, Spain.
Gines M
GM
Salido
Department of Physiology (Cell Physiology Research Group), University of Extremadura, 10003 Cáceres, Spain. Electronic address: jarosado@unex.es.
Juan A
JA
Rosado
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D051379:Mice; D018345:Mice, Knockout; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D000074287:TRPC6 Cation Channel; D013917:Thrombin / Q000494:pharmacology
D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C492146:Trpc6 protein, mouse; D006861:Hydrogen Peroxide; D013917:Thrombin; D003676:Deferoxamine; D002118:Calcium
Aggregation; Calcium; Mouse platelets; OAG; TRPC6; pH