A dynamic set point for thermal adaptation requires phospholipase C-mediated regulation of TRPM8 in vivo

Daniel S. Brenner, Judith P. Golden, Sherri K. Vogt, Ajay Dhaka, Gina M. Story, Robert W. Gereau

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The ability to sense and respond to thermal stimuli at varied environmental temperatures is essential for survival in seasonal areas. In this study, we show that mice respond similarly to ramping changes in temperature from a wide range of baseline temperatures. Further investigation suggests that this ability to adapt to different ambient environments is based on rapid adjustments made to a dynamic temperature set point. The adjustment of this set point requires transient receptor potential cation channel, subfamily member 8 (TRPM8), but not transient receptor potential cation channel, subfamily A, member 1 (TRPA1), and is regulated by phospholipase C (PLC) activity. Overall, our findings suggest that temperature response thresholds in mice are dynamic, and that this ability to adapt to environmental temperature seems to mirror the in vitro findings that PLC-mediated hydrolysis of phosphoinositol 4,5-bisphosphate modulates TRPM8 activity and thereby regulates the response thresholds to cold stimuli.

Original languageEnglish
Pages (from-to)2124-2133
Number of pages10
JournalPain
Volume155
Issue number10
DOIs
StatePublished - Oct 1 2014

Keywords

  • Adaptation
  • Cold
  • Heat
  • PIP2
  • Pain
  • Phospholipase C
  • TRPA1
  • TRPM8
  • Thermosensation

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