Figure 5: Protons potentiate TRPV3 currents in a stimulus-dependent manner.
From: Selective potentiation of 2-APB-induced activation of TRPV1–3 channels by acid
(A) Whole-cell recordings of TRPV3 currents evoked by DPBA. The responses to 5 μM DPBA were remarkably increased by pH 5.5 after sensitization stimulated by repeated applications of 30 μM DPBA. Holding potential was −60 mV. (B) Effects of protons on menthol (Men) and camphor (Cam) activated TRPV3 currents. After sensitization induced by 100 μM 2-APB, the effects of pH 5.5 on currents evoked by Men (1 mM) and Cam (3 mM) were tested. The acidic pH suppressed Men-evoked currents while slowed down the development of Cam-evoked currents without significantly altering the maximal response. Holding potential Vh = −60 mV. (C) Modulation of heat-evoked currents by extracellular protons in HEK293 cells expressing TRPV3 channels. To record heat-activated currents, bath temperatures cycled between the room temperature and ~40 °C multiple times as shown by the temperature trace below. During the heat ramps, bath pH was switched between 7.4 and 5.5. The heat-evoked currents were not significantly altered by pH 5.5. Vh = −60 mV. (D) Comparison of relative changes in current amplitude evoked by various stimuli. Peak currents activated by each stimulus in the presence of pH 5.5 were normalized to the response induced by the same stimulus at pH 7.4. (E) Dose dependence of pH effects on 2-APB response (10 μM). The pH (ranging from 8.5 to 4.5) effects were examined after full sensitization of TRPV3 channel by repeated stimulation with 100 μM 2-APB. Vh = −60 mV. (F) Analysis of dose-response on pH of 2-APB-activated TRPV3 currents. Figure shows averaged data fitted with the Hill equation, which generated a half-maximal pH of 6.70 ± 0.02 and nH = −2.23 ± 0.17 at 10 μM 2-APB (n = 5). Error bars indicate SEM.
