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

Author:

Stratiievska AnastasiiaORCID,Filippova Olga,Özpolat TahsinORCID,Byrne Daire,Bailey S. Lawrence,Chauhan Aastha,Mollica Molly Y.ORCID,Harris Jeff,Esancy KaliORCID,Chen Junmei,Dhaka Ajay K.,Sniadecki Nathan J.ORCID,López José A.,Stolla MoritzORCID

Abstract

The detection of temperature by the human sensory system is life-preserving and highly evolutionarily conserved. Platelets are sensitive to temperature changes and are activated by a decrease in temperature, akin to sensory neurons. 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 multidisciplinary 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.

Funder

NIH

Bloodworks Northwest

American Heart Association

American Society of Hematology

Cerus Corporation

Terumo BCT

Publisher

Public Library of Science (PLoS)

Reference57 articles.

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