Cold temperature induces a TRPM8-independent calcium release from the endoplasmic reticulum in human platelets

Stratiievska, A.; Filippova, O.; Ozpolat, T.; Byrne, D.; Bailey, S. L.; Mollica, M. Y.; Harris, J.; Esancy, K.; Chen, J.; Dhaka, A.; Sniadecki, N. J.; Lopez, J. A.; Stolla, M.

doi:10.1101/2023.07.19.549670

bioRxiv · 10.1101/2023.07.19.549670

Cold temperature induces a TRPM8-independent calcium release from the endoplasmic reticulum in human platelets

Stratiievska, A.·Filippova, O.·Ozpolat, T.·Byrne, D.·Bailey, S. L.·Mollica, M. Y.·Harris, J.·Esancy, K.·Chen, J.·Dhaka, A.·Sniadecki, N. J.·Lopez, J. A.·Stolla, M.

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Abstract

Platelets are sensitive to temperature changes and akin to sensory neurons, are activated by a decrease in temperature. However, the molecular mechanism of this temperature-sensing ability is unknown. Yet, platelet activation by temperature could contribute to numerous clinical sequelae, most importantly to reduced quality of ex vivo-stored platelets for transfusion. In this interdisciplinary study, we present evidence for the expression of the temperature-sensitive ion channel transient receptor potential cation channel subfamily member 8 (TRPM8) in human platelets and precursor cells. We found the TRPM8 mRNA and protein in MEG-01 cells and platelets. Inhibition of TRPM8 prevented temperature-induced platelet activation and shape change. However, chemical agonists of TRPM8 did not seem to have an acute effect on platelets. When exposing platelets to below-normal body temperature, we detected a cytosolic calcium increase which was independent of TRPM8 but was completely dependent on the calcium release from the endoplasmic reticulum. Because of the high interindividual variability of TRPM8 expression, a population-based approach should be the focus of future studies. Our study suggests that the cold response of platelets is complex and TRPM8 appears to play a role in early temperature-induced activation of platelets, while other mechanisms likely contribute to later stages of temperature-mediated platelet response.

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Stratiievska, A., Filippova, O., Ozpolat, T., Byrne, D., Bailey, S. L., Mollica, M. Y., Harris, J., Esancy, K., Chen, J., Dhaka, A., Sniadecki, N. J., Lopez, J. A., Stolla, M.. 2023-07-19. Cold temperature induces a TRPM8-independent calcium release from the endoplasmic reticulum in human platelets. https://doi.org/10.1101/2023.07.19.549670

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