Calcium signaling in platelets

Abstract

Summary. Agonist-induced elevation in cytosolic Ca 2+ concentrations is essential for platelet activation in hemostasis and thrombosis. It occurs through Ca 2+ release from intracellular stores and Ca 2+ entry through the plasma membrane (PM). Ca 2+ store release is a well-established process involving phospholipase (PL)C-mediated production of inositol-1,4,5-trisphosphate (IP 3 ), which in turn releases Ca 2+ from the intracellular stores through IP 3 receptor channels. In contrast, the mechanisms controlling Ca 2+ entry and the significance of this process for platelet activation have been elucidated only very recently. In platelets, as in other non-excitable cells, the major way of Ca 2+ entry involves the agonist-induced release of cytosolic sequestered Ca 2+ followed by Ca 2+ influx through the PM, a process referred to as store-operated calcium entry (SOCE). It is now clear that stromal interaction molecule 1 (STIM1), a Ca 2+ sensor molecule in intracellular stores, and the four transmembrane channel protein Orai1 are the key players in platelet SOCE. The other major Ca 2+ entry mechanism is mediated by the direct receptor-operated calcium (ROC) channel, P2X 1 . Besides these, canonical transient receptor potential channel (TRPC) 6 mediates Ca 2+ entry through the PM. This review summarizes the current knowledge of platelet Ca 2+ homeostasis with a focus on the newly identified Ca 2+ entry mechanisms.

Cyclic nucleotide‐dependent inhibitory signaling interweaves with activating pathways to determine platelet responses

“…IP 3 binds to Ca 2+ channels on the dense tubular system, called IP 3 ‐receptors, resulting in Ca 2+ ‐release into the cytosol followed by store‐operated calcium entry through the plasma membrane ultimately contributing to platelet activation 66. Steady state, ADP‐ and thrombin‐induced elevation of cytosolic Ca 2+ levels have been modelled resulting in the validation of many static and kinetic parameters of the enzymes and ion channels involved 67, 68.…”

Viscoelasticity and Ultrastructure in Coagulation and Inflammation: Two Diverse Techniques, One Conclusion

“…Thrombin-induced activation of platelets initiates degranulation, adhesion and aggregation of platelets resulting in thrombus formation [ 67 ].…”

TxA 2 Receptor‐Based Vaccination: A Novel Potential Therapeutic Approach to Limit Thrombosis

“…This conversion is mediated by phosphatidylserine (PS) exposure from the inner to the outer plasma membrane, which facilitates thrombin/fibrin generation. TxA 2 ‐ and TPR‐mediated signaling induces inositol triphosphate–mediated Ca 2+ store release,19 and it is expected that the C‐EL2 vaccine would potentially alter the Ca 2+ store release and, thus, store‐operated Ca 2+ entry. Nevertheless, it is not clear whether vaccination alters the intracellular levels of Ca2 + and PS exposure, and consequently affects the thrombin/fibrin generation, which is key for hemostasis.…”