(A) Representative heat-evoked inward currents of TRPV1 in control solution and in the presence of 3 mM lidocaine. Currents were evoked by repeated thermal stimuli consisting of a 8-s-long linear rise of temperature from 23°C to 42°C. (B–D) Effect of 3 mM lidocaine on TRPV1 currents activated by 30 nM capsaicin (B), 5 mM camphor (C), or protons (pH 5.8; D). (E) Mean increase of inward currents (percentage ± SEM) measured in experiments described in A–D. In A–D, experiments were performed in Ca²⁺-free extracellular solution and cells were held at –60 mV. (F) Representative TRPV1 currents evoked by 10 mM lidocaine at pH 6.9, 7.4, and 7.9. Test solutions with increasing pH values were applied in intervals of 2 min. Control solution with pH 7.4 and no lidocaine was applied in between. (G) Mean current amplitudes ± SEM measured as described in F and normalized to values obtained at pH 7.4 (paired Student’s t test). (H) Effect of the membrane-impermeable lidocaine derivative QX-314 compared with lidocaine on TRPV1 when applied extracellularly. Cells were held at –60 mV, and 30 mM QX-314 and 30 mM lidocaine were applied for about 10 s in intervals of 2 min. (I) Heat-evoked inward currents of TRPV1 in control solution and in the presence of 3 mM QX-314. Currents were evoked by repeated thermal stimuli as described in A. Note that QX-314 neither activated nor sensitized TRPV1 when applied extracellularly. ***P < 0.001.