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Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices
Published on: October 29, 2012
Menthol suppresses nicotinic acetylcholine receptor functioning in sensory neurons via allosteric modulation
M Hans1, M Wilhelm, D Swandulla
1Department of Physiology, University of Bonn, Nussallee 11, D-53115 Bonn, Germany. michael.hans@ukb.uni-bonn.de
Abstract:
In this study, we have investigated how the function of native and recombinant nicotinic acetylcholine receptors (nAChRs) is modulated by the monoterpenoid alcohol from peppermint (-) menthol. In trigeminal neurons (TG), we found that nicotine (75 μM)-activated whole-cell currents through nAChRs were reversibly reduced by menthol in a concentration-dependent manner with an IC₅₀ of 111 μM. To analyze the mechanism underlying menthol's action in more detail, we used single channel and whole-cell recordings from recombinant human α4β2 nAChR expressed in HEK tsA201 cells. Here, we found a shortening of channel open time and a prolongation of channel closed time, and an increase in single channel amplitude leading in summary to a reduction in single channel current. Furthermore, menthol did not affect nicotine's EC₅₀ value for currents through recombinant human α4β2 nAChRs but caused a significant reduction in nicotine's efficacy. Taken together, these findings indicate that menthol is a negative allosteric modulator of nAChRs.
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