Regulation of the cold-sensing TRPM8 channels by phosphoinositides and Gq-coupled receptors

Channels (Austin). 2020 Dec;14(1):79-86. doi: 10.1080/19336950.2020.1734266.


The Transient Receptor Potential Melastatin 8 (TRPM8) ion channel is an important sensor of environmental cold temperatures. Cold- and menthol-induced activation of this channel requires the presence of the membrane phospholipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. This review discusses recent findings on the role of PI(4,5)P2 and G-proteins in the modulation of TRPM8 upon receptor activation. We will also summarize knowledge on the role of PI(4,5)P2 in Ca2+ dependent desensitization/adaptation of TRPM8 activity, and recent advances in the structural basis of how this lipid binds to TRPM8.

Keywords: G-alpha-q; GPCR; PIP2; TRPM8; phosphoinositides.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cold Temperature
  • Humans
  • Phosphatidylinositol 4,5-Diphosphate / metabolism
  • Phosphatidylinositols / metabolism*
  • TRPM Cation Channels / genetics
  • TRPM Cation Channels / metabolism*
  • Transient Receptor Potential Channels / metabolism*


  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositols
  • TRPM Cation Channels
  • TRPM8 protein, human
  • Transient Receptor Potential Channels