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

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)P-2]. This review discusses recent findings on the role of PI(4,5)P-2 and G-proteins in the modulation of TRPM8 upon receptor activation. We will also summarize knowledge on the role of PI(4,5)P-2 in Ca2+ dependent desensitization/adaptation of TRPM8 activity, and recent advances in the structural basis of how this lipid binds to TRPM8.