Figure 7: Protons enhance the inhibitory effects of 2-APB on TRPM8 channels.
From: Selective potentiation of 2-APB-induced activation of TRPV1–3 channels by acid
(A) Inhibition of TRPM8 by 2-APB. Representative whole-cell currents at −60 mV recorded from TRPM8-expressing HEK293 cells, showing that acid (pH 5.5 and 6.0) potentiated the inhibitory effect of 2-APB on menthol (Men, 100 μM)-evoked currents. Note, acid alone only caused weak inhibition (~19% and ~29% at pH 6.0 and 5.5, respectively), but it strongly enhanced the inhibition by 10 μM 2-APB with slow kinetics. (B) Summary of relative currents elicited by 100 μM Men at pH 7.4 (not indicated), 6.0, or 5.5 in the absence or presence of 2-APB as indicated. The steady-state response was normalized to the peak current evoked by 100 μM Men for each cell. (C) Concentration-response to 2-APB at pH 7.4 and 5.5 for currents elicited by 100 μM Men. Data were fitted by the Hill equation and yielded: IC50 = 20.53 ± 3.28 μM and nH = 1.41 ± 0.28 for pH 7.4 (n = 8) and IC50 = 3.07 ± 0.09 μM and nH = 1.49 ± 0.08 for pH 5.5 (n = 10). Error bars indicate SEM.
