Figure 1.

Ca²⁺ signaling in procoagulant platelets

Platelet activators, such as collagen and thrombin, trigger a cytosolic Ca²⁺ signal (1) through Ca²⁺ release from intracellular stores and Ca²⁺ entry through plasma membrane channels. The magnitude and temporal nature of these signals varies between platelets. The cytosolic Ca²⁺ signals promote platelet aggregation by regulating granule secretion and integrin α_IIbβ₃ activation (not shown). Some cytosolic Ca²⁺ is taken into mitochondria via MCU, increasing mitochondrial Ca²⁺ concentration ([Ca²⁺]_mito). In some platelets, [Ca²⁺]_mito exceeds the threshold for permeability transition pore opening (2). This triggers a ‘supramaximal’ cytosolic Ca²⁺ signal in these platelets (3), which are now committed to becoming procoagulant platelets. The supramaximal Ca²⁺ signal activates the TMEM16F, the phospholipid scramblase, resulting in phosphatidylserine exposure on the outer surface of procoagulant platelets.