Platelet calcium homeostasis

Ca2+ homeostasis is controlled by processes that elevate or counter the elevation of cytosolic Ca2+. During steady state conditions, cytoplasmic Ca2+ is reduced by the accumulation of Ca2+ in intracellular stores and by Ca2+ extrusion. The primary intracellular calcium store in platelets is the dense tubular system, the equivalent of the ER system in other cell types. Ca2+ is extruded by Ca2+-ATPases including plasma membrane Ca2+ ATPases (PMCAs) and sarco/endoplasmic reticulum Ca2+ -ATPase isoforms (SERCAs). <br><br>Activation of non- excitable cells involves the agonist-induced elevation of cytosolic Ca2+, an essential process for platelet activation. It occurs through Ca2+ release from intracellular stores and Ca2+ entry through the plasma membrane. Ca2+ store release involves phospholipase C (PLC)-mediated production of inositol-1,4,5-trisphosphate (IP3), which in turn stimulates IP3 receptor channels to release Ca2+ from intracellular stores. This is followed by Ca2+ entry into the cell through plasma membrane calcium channels, a process referred to as store-operated calcium entry (SOCE). Stromal interaction molecule 1 (STIM1), a Ca2+ sensor molecule in intracellular stores, and the four transmembrane channel protein Orai1 are the key players in platelet SOCE. Other major Ca2+ entry mechanisms are mediated by the direct receptor-operated calcium (ROC) channel, P2X1 and transient receptor potential channels (TRPCs).

细胞内钙离子稳态的维持，依赖于提升或抑制细胞质钙离子升高的过程。在稳态条件下，细胞质钙离子浓度通过细胞内储存的钙离子积累以及钙离子的外排作用而降低。在血小板中，密集管道系统作为主要的细胞内钙储存库，相当于其他细胞类型中的内质网系统。钙离子的外排由钙离子-ATP酶负责，包括质膜钙离子ATP酶（PMCAs）和横纹/内质网钙离子-ATP酶同型（SERCAs）。非兴奋性细胞的激活涉及激动剂诱导的细胞质钙离子升高，这一过程对于血小板的激活至关重要。其发生机制为钙离子从细胞内储存的释放以及通过质膜进入细胞。钙离子储存释放涉及磷脂酶C（PLC）介导的肌醇-1,4,5-三磷酸（IP3）的产生，进而刺激IP3受体通道释放细胞内储存的钙离子。随后，钙离子通过质膜钙离子通道进入细胞，这一过程被称为储存操作钙离子进入（SOCE）。间质相互作用分子1（STIM1），作为细胞内储存库中的钙离子传感器分子，以及四个跨膜通道蛋白Orai1，是血小板SOCE中的关键作用者。其他主要的钙离子进入机制则由直接受体操作钙离子（ROC）通道、P2X1和瞬时受体电位通道（TRPCs）介导。