Store-operated calcium entry and non-capacitative calcium entry have distinct roles in thrombin-induced calcium signalling in human platelets
Store-operated calcium entry and non-capacitative calcium entry have distinct roles in thrombin-induced calcium signalling in human platelets
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DOI：
10.1016/j.ceca.2011.06.005
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发表时间：
2011-10-01
期刊：
影响因子：
4
通讯作者：
Poole, Alastair W.
中科院分区：
文献类型：
--
作者：
Harper, Matthew T.;Poole, Alastair W.
暴露于磷脂酰丝氨酸（PS）的血小板加速血管损伤部位的凝血。PS暴露需要持续的Ca 2+信号传导。两种不同的Ca 2+进入途径放大和维持血小板Ca 2+信号传导，但它们在人类血小板中的相对重要性尚不清楚。在这里，我们研究了相对作用的钙池操作的Ca 2+内流（SOCE）和非容量性Ca 2+内流（NCCE）凝血酶诱导的Ca 2+信号和PS曝光使用两个Ca 2+通道阻滞剂。BTP-2对SOCE的选择性明显高于NCCE。在我们的条件下，LOE-908特异性阻断NCCE。使用这些药物，我们发现，SOCE是重要的，在低凝血酶浓度，而NCCE变得越来越重要，随着凝血酶浓度的增加。PS暴露被LOE-908降低，并且仅在也激活NCCE的凝血酶浓度下被激活。相反，BTP-2对PS暴露没有影响。我们认为，SOCE放大和维持Ca 2+信号在低浓度的凝血酶，而NCCE和SOCE是重要的贡献者在较高的凝血酶浓度的Ca 2+信号。然而，尽管在高凝血酶浓度下参与Ca 2+信号传导，但SOCE对凝血酶诱导的人血小板PS暴露并不重要。这表明Ca 2+进入途径是凝血酶诱导的血小板PS暴露的重要调节因子。(C)2011爱思唯尔有限公司版权所有。
Phosphatidylserine (PS)-exposing platelets accelerate coagulation at sites of vascular injury. PS exposure requires sustained Ca2+ signalling. Two distinct Ca2+ entry pathways amplify and sustain platelet Ca2+ signalling, but their relative importance in human platelets is not known. Here we examined the relative roles of store-operated Ca2+ entry (SOCE) and non-capacitative Ca2+ entry (NCCE) in thrombin-induced Ca2+ signalling and PS exposure by using two Ca2+ channel blockers. BTP-2 showed marked selectivity for SOCE over NCCE. LOE-908 specifically blocked NCCE under our conditions. Using these agents we found that SOCE is important at low thrombin concentrations whereas NCCE became increasingly important as thrombin concentration was increased. PS exposure was reduced by LOE-908, and only activated at thrombin concentrations that also activate NCCE. In contrast, BTP-2 had no effect on PS exposure. We suggest that SOCE amplifies and sustains Ca2+ signalling in response to low concentrations of thrombin whereas both NCCE and SOCE are important contributors to Ca2+ signalling at higher thrombin concentrations. However, despite being involved in Ca2+ signalling at high thrombin concentrations, SOCE is not important for thrombin-induced PS exposure in human platelets. This suggests that the route of Ca2+ entry is an important regulator of thrombin-induced PS exposure in platelets. (C) 2011 Elsevier Ltd. All rights reserved.