Mouse transient receptor potential channel type 6 selectively regulates agonist-induced platelet function

Enma V. Paez Espinosa, Olivia A. Lin, Zubair A. Karim, Fatima Z. Alshbool, Fadi T. Khasawneh

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


While changes in intracellular calcium levels is a central step in platelet activation and thrombus formation, the contribution and mechanism of receptor-operated calcium entry (ROCE) via transient receptor potential channels (TRPCs) in platelets remains poorly defined. In previous studies, we have shown that TRPC6 regulates hemostasis and thrombosis, in mice. In the present studies, we employed a knockout mouse model system to characterize the role of TRPC6 in ROCE and platelet activation. It was observed that the TRPC6 deletion (Trpc6−/−) platelets displayed impaired elevation of intracellular calcium, i.e., defective ROCE. Moreover, these platelets also exhibited defects in a host of functional responses, namely aggregation, granule secretion, and integrin αIIbβ3. Interestingly, the aforementioned defects were specific to the thromboxane receptor (TPR), as no impaired responses were observed in response to ADP or the thrombin receptor-activating peptide 4 (TRAP4). The defect in ROCE in the Trpc6−/− was also observed with 1-oleoyl-2-acetyl-sn-glycerol (OAG). Finally, our studies also revealed that TRPC6 regulates clot retraction. Taken together, our findings demonstrate that TRPC6 directly regulates TPR-dependent ROCE and platelet function. Thus, TRPC6 may serve as a novel target for the therapeutic management of thrombotic diseases.

Original languageEnglish (US)
Article number100685
JournalBiochemistry and Biophysics Reports
StatePublished - Dec 2019
Externally publishedYes


  • Calcium channel
  • Platelets
  • Receptor-operated calcium entry
  • TRPC6

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry


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