G _αq Sensitizes TRPM8 to Inhibition by PI(4,5)P₂ Depletion upon Receptor Activation.

ABSTRACT: The cold- and menthol-sensitive transient receptor potential melastatin 8 (TRPM8) channel is important for both physiological temperature detection and cold allodynia. Activation of G-protein-coupled receptors (GPCRs) by proinflammatory mediators inhibits these channels. It was proposed that this inhibition proceeds via direct binding of G _αq to the channel. TRPM8 requires the plasma membrane phospholipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂ or PIP₂] for activity. However, it was claimed that a decrease in cellular levels of this lipid upon receptor activation does not contribute to channel inhibition. Here, we show that supplementing the whole-cell patch pipette with PI(4,5)P₂ reduced inhibition of TRPM8 by activation of G

SUBMITTER: Liu L 

PROVIDER: S-EPMC6668199 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature