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The Journal of Neuroscience, September 12, 2007, 27(37):9874-9884; doi:10.1523/JNEUROSCI.2221-07.2007
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Cellular/Molecular
Bimodal Action of Menthol on the Transient Receptor Potential Channel TRPA1
Yuji Karashima, * Nils Damann, * Jean Prenen, Karel Talavera, Andrei Segal, Thomas Voets, andBernd Nilius Laboratorium voor Fysiologie, Campus Gasthuisberg, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium
Correspondence should be addressed to Nils Damann, Department of Physiology, Campus Gasthuisberg, Katholieke Universiteit Leuven, Herestraat 49, B-3000 Leuven, Belgium. Email: nils.damann{at}med.kuleuven.be
TRPA1 is a calcium-permeable nonselective cation transient receptor potential (TRP) channel that functions as an excitatory ionotropic receptor in nociceptive neurons. TRPA1 is robustly activated by pungent substances in mustard oil, cinnamon, and garlic and mediates the inflammatory actions of environmental irritants and proalgesic agents. Here, we demonstrate a bimodal sensitivity of TRPA1 to menthol, a widely used cooling agent and known activator of the related cold receptor TRPM8. In whole-cell and single-channel recordings of heterologously expressed TRPA1, submicromolar to low-micromolar concentrations of menthol cause channel activation, whereas higher concentrations lead to a reversible channel block. In addition, we provide evidence for TRPA1-mediated menthol responses in mustard oil-sensitive trigeminal ganglion neurons. Our data indicate that TRPA1 is a highly sensitive menthol receptor that very likely contributes to the diverse psychophysical sensations after topical application of menthol to the skin or mucous membranes of the oral and nasal cavities.
Key words: TRP channels; trigeminal neurons; pain; chemosensation; menthol; mustard oil
Received March 2, 2007; revised July 13, 2007; accepted July 14, 2007.
Correspondence should be addressed to Nils Damann, Department of Physiology, Campus Gasthuisberg, Katholieke Universiteit Leuven, Herestraat 49, B-3000 Leuven, Belgium. Email: nils.damann{at}med.kuleuven.be
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