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Regulation of TRPM8 by PI(4,5)P2 and G-proteins During GPCR activation, the Gαq subunit stimulates PLCβ isoforms that induce a decrease of plasma membrane PI(4,5)P2 levels which limits TRPM8 activity. Gαq also directly binds to the channel and inhibits its activity (left side of cartoon). Ca2+ entering through the channel stimulates PLCδ isoforms, which leads to a decrease in PI(4,5)P2 levels and inhibits channel activity (right side of cartoon). See main text for details.
