TRPM8 is inhibited more efficiently by PI(4,5)P2 depletion in the presence of Gαq. A, B, Representative whole-cell voltage-clamp traces of inward currents recorded at −60 mV from HEK 293 cells transfected with TRPM8 and the voltage-sensitive phosphatase CiVSP (A) or with ciVSP, TRPM8, and 3GqiqQ209L (B). Measurements were conducted in Ca2+-free NCF solution. TRPM8 channels were activated by 500 μm menthol. CiVSP was activated by +100 mV steps for 0.1, 0.2, 0.3, and 1 s. C, Summary of raw current densities before the application of voltage steps (peak) and after voltage steps to +100 mV for 0.1, 0.2, 0.3, and 1 s for each group; n = 7 for TRPM8 + CiVSP and n = 9 for TRPM8 + CiVSP + 3GqiqQ209L (two-way ANOVA, F(9,70) = 5.40, p = 1.3 × 10−5). D. Summary of the same data expressed as current inhibition induced by voltage steps. Bars represent mean ± SEM; statistical significance was calculated with two-way ANOVA (F(7,56) = 13.66, p = 3.7 × 10−10).