Figure 1.

Alpha-mangostin (α-MG) inhibited the TRPV3 current. Currents were elicited with ramp pulses from −100 to +100 mV over 1 s, which was repetitively applied every 20 s; the holding potential was set at 0 mV. (A) Alpha-mangostin inhibited 2-APB-evoked current in a representative TRPV3 overexpressing HEK 293T cell. The channel was activated using 100 µM 2-APB and subsequently perfused with solutions containing different concentrations of alpha-mangostin with 100 µM 2-APB. A solution containing 10 µM ruthenium red (RR, a TRP channel inhibitor) and 100 µM 2-APB was perfused at the end. (B) The dose–response curve of TRPV3 current inhibition by alpha-mangostin (IC₅₀ = 0.077 ± 0.013 µM). Currents were normalized to the maximum response to 2-APB at −100 mV. (C) Alpha-mangostin inhibited carvacrol-evoked current in a representative TRPV3-overexpressing HEK 293T cell. TRPV3 was activated using 1000 µM carvacrol and subsequently perfused with solutions containing different concentrations of alpha-mangostin with 1000 µM carvacrol. A solution containing 10 µM RR and 1000 µM carvacrol was perfused at the end. (D) Summary of normalized currents evoked by carvacrol with or without alpha-mangostin at −100 mV. Currents were normalized to the maximum response carvacrol at −100 mV. (E) Alpha-mangostin inhibited 2-APB-evoked current in NHEK. The channel was activated using 100 µM 2-APB and subsequently perfused with solutions containing different concentrations of alpha-mangostin with 100 µM 2-APB. A solution containing 10 µM 74a (a TRPV3 inhibitor) and 100 µM 2-APB was perfused at the end. The left panel shows the current–voltage relationship; I_max represents the maximum response to 100 µM 2-APB at +100 mV. The right panel summarizes normalized currents evoked by 2-APB with or without alpha-mangostin at −100 mV. Currents were normalized to the maximum response to 2-APB at −100 mV. Data are presented as means ± SEM. ** p < 0.01, *** p < 0.001, **** p < 0.0001.