Referenced in: none

Automatically associated channels: TRP , TRPC , TRPC3 , TRPC6

Title: A role for platelet TRPC channels in the Ca2+ response that induces procoagulant activity.

Authors: Martyn P Mahaut-Smith

Journal, date & volume: Sci Signal, 2013 Jun 25 , 6, pe23

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23800467

Abstract
After vascular injury, platelets are rapidly activated by collagen and other agonists, causing them to adhere and aggregate to prevent blood loss. In addition, phosphatidylserine (PS) exposure on the platelet surface accelerates thrombin formation by the coagulation pathway. Thrombin is a potent platelet agonist and converts fibrinogen to fibrin, thereby stabilizing the platelet plug. PS exposure during hemostasis and thrombosis results from a sustained cytosolic Ca(2+) increase; however, the underlying Ca(2+) mobilization pathways have remained unclear. Store-operated Orai1 channels provide substantial, prolonged Ca(2+) influx after inositol trisphosphate-dependent release, and anoctamin 6 (TMEM16F) may operate as a Ca(2+)-activated, Ca(2+)-permeable channel in addition to its scramblase activity that exteriorizes PS. A new study shows that Na(+) entry, resulting from coactivation of the transient receptor potential (TRP) nonselective cation channels TRPC3 and TRPC6, followed by reverse-mode operation of Na(+)/Ca(2+) exchangers, is an important mechanism for the increase in cytosolic Ca(2+) that triggers PS exposure, particularly during combined thrombin and collagen stimulation.