Department of Cell Physiology and Pharmacology, University of Leicester, Leicester LE1 9HN, UK.
Sci Signal. 2013 Jun 25;6(281):pe23. doi: 10.1126/scisignal.2004399.
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.
血管损伤后，血小板被胶原蛋白和其他激动剂迅速激活，导致它们黏附和聚集以防止失血。此外，血小板表面的磷脂酰丝氨酸（PS）暴露加速了凝血途径中的凝血酶形成。凝血酶是一种有效的血小板激动剂，将纤维蛋白原转化为纤维蛋白，从而稳定血小板栓子。止血和血栓形成过程中 PS 的暴露是由于细胞浆 Ca(2+)持续增加所致；然而，潜在的 Ca(2+)动员途径仍不清楚。储存操纵性 Orai1 通道在肌醇三磷酸依赖性释放后提供大量、延长的 Ca(2+)内流，而 anoctamin 6（TMEM16F）除了其外翻 PS 的裂合酶活性外，还可能作为一种 Ca(2+)激活的、Ca(2+)渗透性通道发挥作用。一项新的研究表明，Na(+)的进入，源自瞬时受体电位（TRP）非选择性阳离子通道 TRPC3 和 TRPC6 的共同激活，随后是 Na(+)/Ca(2+)交换器的反向模式操作，是触发 PS 暴露的细胞浆 Ca(2+)增加的重要机制，尤其是在凝血酶和胶原蛋白联合刺激期间。
