PathwayStep541 PathwayStep545 Reduction of cytosolic Ca++ levels Platelet calcium homeostasis Authored: Akkerman, JW, 2009-06-03 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). Edited: Jupe, S, 2010-06-07 Pubmed18308196 Pubmed19422456 Reactome Database ID Release 43418360 Reactome, http://www.reactome.org ReactomeREACT_23905 Reviewed: Kunapuli, SP, 2010-06-07 Elevation of cytosolic Ca2+ levels