Fig. 1: Menthol blocks rabbit TRPV5 channels.
From: Molecular mechanism of menthol-induced TRPV5 channel inhibition
a Currents in response to voltage-clamp steps of 200 ms durations from −150 to 50 mV. Left panel in the absence and right panel in the presence of 500 μM menthol. b Current-voltage relationship of currents as in (a). Black circles, control; blue circles, menthol, n = 6 independent membrane patches. Data are shown as mean ± SEM. c Representative current traces of rbTRPV5 channels from an outside-out patch at −100 mV with increasing concentrations of menthol. Light blue trace was obtained by applying recording solution containing only 1.5% ethanol (vehicle) as a control. The rest of the traces are currents in the presence of increasing menthol concentration. d Time course of rbTRPV5-mediated current inhibition by menthol at increasing concentrations applied to the outside-out patch in (c). e Dose-response curve obtained from n = 7 outside-out patch recordings. The black curve is the fit to the Hill equation (Eq. 1) with the parameters IC50 = 142.6 μM ± 18.3 μM and Hill coefficient, nH = 0.75 ± 0.064. The dotted curve is the fit to the dose response predicted by Scheme I in (g) at −100 mV (Supplementary Note, Eqs. (4–7)). f Current-voltage relationships at 0 mM (diamonds), 3 mM (squares), 500 μM (circles) and 100 μM (triangles) menthol plotted in the interval -150 to −50 mV. Symbols are the mean of n = 6 independent outside-out patches. Shaded areas indicating the SEM. g The fraction of current blocked as a function of voltage at 3 mM (squares), 500 μM (circles) and 100 μM (triangles) menthol. Symbols are the mean of n = 6 independent outside-out patches. Shaded areas indicating the SEM. The dashed lines are the predicted blocked fractions at the indicated menthol concentration. The parameters of the model K1(0) = 0.2; K2(0) = 0.22, q1 = −0.1 eo, q2 = −0.6 eo, KD = 140 μM.
