Ashoor_2013_PLoS.One_8_e67674

Menthol is a common compound in pharmaceutical and commercial products and a popular additive to cigarettes. The molecular targets of menthol remain poorly defined. In this study we show an effect of menthol on the alpha7 subunit of the nicotinic acetylcholine (nACh) receptor function. Using a two-electrode voltage-clamp technique, menthol was found to reversibly inhibit alpha7-nACh receptors heterologously expressed in Xenopus oocytes. Inhibition by menthol was not dependent on the membrane potential and did not involve endogenous Ca(2+)-dependent Cl(-) channels, since menthol inhibition remained unchanged by intracellular injection of the Ca(2+) chelator BAPTA and perfusion with Ca(2+)-free bathing solution containing Ba(2+). Furthermore, increasing ACh concentrations did not reverse menthol inhibition and the specific binding of [(125)I] alpha-bungarotoxin was not attenuated by menthol. Studies of alpha7- nACh receptors endogenously expressed in neural cells demonstrate that menthol attenuates alpha7 mediated Ca(2+) transients in the cell body and neurite. In conclusion, our results suggest that menthol inhibits alpha7-nACh receptors in a noncompetitive manner.