Mouse transient receptor potential channel 6: role in hemostasis and thrombogenesis.
Although changes in the intracellular levels of calcium (Ca(2+)) are a central step in platelet activation, the underlying mechanism of Ca(2+) entry is still unclear. Previous studies have demonstrated that TRPC6, a member of the canonical transient receptor potential channel (TRPC) family is expressed in platelets in a significant amount, and is predominantly found on the plasma membrane. Based on these considerations, we hypothesized that TRPC6 plays a critical role in platelet function. To characterize the role of TRPC6 in platelet function in vivo, we employed a genetic approach, subjecting TRPC6 knockout mice to the tail bleeding time test and a carotid artery injury thrombosis model. We found that TRPC6-deficient animals displayed a prolonged bleeding time, and an increased time for occlusion of the injured carotid artery, compared to their wild-type littermates. Taken together, our data demonstrate for the first time, that TRPC6 deletion in mice results in defects in hemostasis and protection against thrombogenesis, suggesting a vital role in platelet function. Furthermore, TRPC6 may define a new therapeutic target for managing multiple thrombosis-based disorders.
Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
Enma V
EV
Paez Espinosa
John P
JP
Murad
Harold J
HJ
Ting
Fadi T
FT
Khasawneh
D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D017353:Gene Deletion; D006487:Hemostasis / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D050052:TRPC Cation Channels / Q000235:genetics / Q000502:physiology*; D000074287:TRPC6 Cation Channel; D013927:Thrombosis / Q000097:blood* / Q000235:genetics*
D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C492146:Trpc6 protein, mouse