[Calcium signaling in platelet activation]

The activation of platelet is the initial factor for natural hemostasis and thrombosis and the elevation in intracellular free calcium concentration ([Ca2+]i) plays a key role in platelet activation. The increased [Ca2+]i is due to the entry of extracellular Ca2+ through the plasma membrane (PM) and the release of intracellular Ca2+ through Ca2+ pools, which are divided mainly into two types: one is the dense tubular system (DTS), and the other is lysosome-like acidic organelles (LLAO). The former releases calciums via the signal transduction pathway of inositol-1,4,5-trisphosphate (IP3), and the latter via nicotinic acid adenine dinucleotide phosphate (NAADP). Sequentially, store-operated calcium channels (SOCC) are responsible for most of calcium influx from extracellular compartment, which is regulated by the cooperation of stromal interaction molecule 1 (STIM1), a Ca2+ sensor molecule in intracellular stores, and ORAI calcium release-activated calcium modulator 1 (Orail), a plasma membrane protein. Their regulation will emplify the results of elevation of [Ca2+]i. There are two different pumps to remove the intracellular free Ca2+ after the elevation of [Ca2+]i, one is sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA) to pump Ca2+ back to the intracellular stores, the other is the plasma membrane Ca2+ ATPase (PMCA) which pumps Ca2+ out of the cells, to maintain low intracellular calcium concentration relatively in the resting.