Effects of voltage and temperature on TRPM8 whole-cell currents. (A) I-V relationships measured using voltage ramps (from 200 to −100 mV during 1 s) for temperatures ranging from 35 to 19°C in 1°C steps. (B) TRPM8 activation curves (gray traces) at different temperatures obtained by dividing current amplitude by driving force at each potential and fitted with the Boltzmann equation (with a best-fit shared slope factor of −38.5 mV) as shown by the superimposed smooth black lines. Cooling increases G_max and shifts activation to the left. (C) Best-fit G_max values decrease with increasing temperature in a sigmoidal manner with a t_1/2 of 30.6°C. (D) V_1/2 increases with increasing temperature in a sigmoidal manner with a t_1/2 of 25.5°C. (E) Normalized current (I/I_max) at 80, 140, and 200 mV plotted against temperature. The ratio of leak-corrected whole-cell TRPM8 currents measured at 20 and 30°C and at 120 mV was 3.90 ± 0.85, with values ranging from 1.57 to 8.76 (n = 10). (F) The temperature for half-maximal activation increases with voltage, with the temperature sensitivity appearing to saturate at lower potentials.