Menthol produces cold sensations by eliciting afferent impulses in cold receptors, which is ascribed to an activation of the TRP channel TRPM8. We investigated menthol effects on the firing rate (FR) of temperature-sensitive hypothalamic neurons and also demonstrated the existence of TRPM8 mRNA transcripts in the rat hypothalamus using quantitative RT-PCR. Identification of TRPM8 expressing neurons by ISH is in progress. In the electrophysiological experiments most cells increased their FR on warming and decreased the FR on cooling. After application of menthol (100mM-2mM) most of the warm-sensitive neurons showed a decrease of their basal FR. This is in analogy to the concept of menthol as an agent that mimics cooling. However, activation of TRPM8 should lead to a depolarization by Ca²⁺ influx, which is in contrast to the observed inhibition. Therefore we hypothesize further (e.g. Ca²⁺ dependent K⁺ channels) or different mechanisms to account for the menthol-induced inhibition of warmsensitive hypothalamic neurons despite of the depolarization which should be expected from pure TRPM8 effects.

This work was supported by the EU through the Network of Excellence BioSim, Contract No. LSHB-CT-2004-005137.