Figure 6.

The S29A mutant recapitulates the alterations in the biophysical phenotype induced by kinase activity inhibition. A, Representative recordings of whole-cell currents measured at 100 and −60 mV in HEK293 transfected with mTRPM8-myc (open black circles) and S29A mTRPM8-myc (open magenta circles) channels. B, Scatter plots with mean and SD of maximal current density at 100 and −60 mV. Statistical significance was assessed with a two-tailed unpaired Student's t test with Welch's correction (Cold_100mV: t₍₃₇₎ = 4.64, p < 0.0001; Menthol_100mV: t₍₃₅₎ = 2.79, p = 0.0086; Cold+menthol_100mV: t₍₃₇₎ = 2.35, p = 0.0241; Cold_-60mV: t₍₂₅₎ = 3.54, p = 0.0016; Menthol_-60mV: t₍₃₇₎ = 2.18, p = 0.0357; Cold+menthol_-60mV: t₍₃₇₎ = 3.02, p = 0.0046). C, I–V relationships in Control (Ctrl.), Cold (C), Menthol (M), and Cold+menthol (C + M) conditions of cells in A. D, Scatter plots with mean and SD of the V_1/2 values. E, Scatter plots with mean and SD g_max values estimated in Cold+menthol condition. Statistical significance was assessed with a two-tailed unpaired Student's t test with Welch's correction (V_1/2 cold: t₍₃₇₎ = 6.58, p < 0.0001; V_1/2 menthol: t₍₃₃₎ = 4.23, p = 0.0002; V_1/2 Cold+menthol: t₍₃₃₎ = 2.23, p = 0.0325; g_max: t₍₃₃₎ = 2.22, p = 0.0334). *p < 0.05; **p < 0.01; ***p < 0.001; n > 15 cells for each condition.