Capsaicin concentration-dependent activation of rat TRPV1 is shifted to the left under acidic conditions. Capsaicin potency is increased ~10 fold when the pH of the capsaicin-containing external solution is dropped from pH 7.4 (EC50 = 640 nM, closed squares) to pH 5.5 (45 nM, open circles). Currents evoked by application of pH 5.5 alone or that were required to hold the cell at -60 mV (resting holding current) were subtracted from peak responses. Data are the normalized average (mean ± SEM) of the resulting maximal currents for each condition. Inset) Peak responses of currents evoked by 30 μM capsaicin were compared at pH 7.4 and pH 5.5 on the same cell. No difference was detected in these experiments indicating that acidic conditions did not alter the efficacy of capsaicin. Data are the mean ± SEM.