Calcium influx pathways in platelets

Calcium influx pathways in platelets are critical mechanisms that regulate the elevation of cytosolic calcium concentration ([Ca2+]i), a central event in platelet activation, aggregation, and procoagulant activity (Varga-Szabo et al., 2009; Varga-Szabo et al., 2011). The primary pathway is store-operated calcium entry (SOCE), which is mediated by the endoplasmic reticulum (ER) calcium sensor STIM1 and the plasma membrane channel ORAI1 (Lopez et al., 2009; Gilio et al., 2010). Upon depletion of intracellular calcium stores (the dense tubular system), STIM1 undergoes a conformational change and translocates to the plasma membrane to activate ORAI1, allowing extracellular calcium to enter the cell (Varga-Szabo et al., 2011; van Kruchten et al., 2012). Other pathways include receptor-operated calcium entry (ROCE) via P2X1 and TRPC6 channels, as well as mitochondrial calcium influx through the mitochondrial calcium uniporter (MCU) (Remenyi et al., 2011; Varga-Szabo et al., 2009). These pathways are essential for thrombus formation and stability; however, their overactivation is linked to cardiovascular diseases such as thrombosis, stroke, and myocardial infarction (Gilio et al., 2010; Zbidi et al., 2009). Pharmacological inhibition of these pathways, particularly SOCE, is being explored as a strategy to develop novel antiplatelet agents with potentially lower bleeding risks than current therapies, although concerns regarding systemic effects on immune function remain (Gilio et al., 2010; NIH/PMC).

Other names

Store-operated calcium entrySOCEReceptor-operated calcium entryROCECalcium entry pathwaysPlatelet calcium signaling

Inhibition of store-operated calcium entry (SOCE) and receptor-operated calcium entry (ROCE) to reduce intracellular calcium levels and prevent platelet activation and thrombus formation.