Figure 2.

Nicotinic acid activates mTRPV1 at room temperature. (A) Molecular structures of nicotinic acid and capsaicin. (B) Nicotinic acid (pH 7.4) directly activates TRPV1 from the intracellular side but not from the extracellular side. Representative recordings with nicotinic acid in the pipette solution (left) or in perfusion solution (right) using the indicated patch configurations. (C) Nicotinic acid dose-response curves before (open circle) and after (filled circle) correction for the change in single-channel conductance. Superimposed are fits of a Hill equation with (before correction, black) EC₅₀ = 62.34 ± 0.75 mM, slope factor = 2.87 ± 0.09 (n = 4), and (after correction, gray) EC₅₀ = 53.9 ± 1.81 mM, slope factor = 3.53 ± 0.32 (n = 4). (D) Representative currents showing the relative efficacy of nicotinic acid and capsaicin as agonists. (E) Quantitative summary of the efficacy of 130 mM Nicotinic acid relative to 10 μM capsaicin on TRPV1 activation (n = 4). (F) Representative single-channel current traces activated by nicotinic acid at the indicated concentrations. (G) Box-and-whisker plot of conductance measurements. The whisker top, box top, line inside the box, box bottom, and whisker bottom represent the maximum, 75^th percentile, median, 25^th percentile, and minimum value of each pool of conductance measurements, respectively. n = 4. ***, p < 0.001; n.s., not significant.