The Transient Receptor-Potential Channel 6 Plays a Critical Role In Platelet Function Academic Article uri icon


  • Abstract Abstract 3201 In spite of the fact that changes in the intracellular levels of calcium (e.g., calcium entry (CE)) is a central step in platelet activation, the underlying mechanism of this CE is still ill defined. Previous studies have demonstrated that of the transient receptor potential channel (TRPC) family, TRPC1 and, to a higher extent, TRPC6 are expressed in blood platelets, whereas TRPC4 is found in megakaryocytes (at the mRNA level). Furthermore, recent studies have shown that TRPC1 deficient platelets exhibited no defects in platelet function, and unaltered calcium homeostasis. Based on these considerations, we hypothesized that TRPC6 plays an essential role in receptor-operated calcium entry and platelet function. Our preliminary studies reveal that platelets deficient in TRPC6 exhibited a defect in platelet aggregation mediated by the thromboxane receptor (TPR), at least, at low agonist levels (i.e., low levels of receptor activation). Moreover, TRPC6 deficient mice also exhibited a significantly prolonged bleeding time, and were protected against thrombosis development, using a FeCl3 carotid-artery injury model. Together, these findings are consistent with the role of TPRs in hemostasis and the genesis of thrombosis. In future studies, we will investigate the role of TRPC6 in: 1. calcium homeostasis; 2. separate platelet functional responses such as dense granule secretion and shape change; and 3. in platelet activation via separate platelet G-protein coupled receptors such as PAR4 and P2Y1. These studies may define a new therapeutic target for managing multiple thrombosis-based disorders. Disclosures: No relevant conflicts of interest to declare.

published proceedings

  • Blood

author list (cited authors)

  • Murad, J. P., Ting, H. J., & Khasawneh, F. T.

citation count

  • 0

complete list of authors

  • Murad, John P||Ting, Harold J||Khasawneh, Fadi T

publication date

  • November 2010

published in