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Heat activation of TRPM5 underlies thermal sensitivity of sweet taste


TRPM5, a cation channel of the TRP superfamily, is highly expressed in taste buds of the tongue, where it has a key role in the perception of sweet, umami and bitter tastes1,2. Activation of TRPM5 occurs downstream of the activation of G-protein-coupled taste receptors and is proposed to generate a depolarizing potential in the taste receptor cells2. Factors that modulate TRPM5 activity are therefore expected to influence taste. Here we show that TRPM5 is a highly temperature-sensitive, heat-activated channel: inward TRPM5 currents increase steeply at temperatures between 15 and 35 °C. TRPM4, a close homologue of TRPM5, shows similar temperature sensitivity. Heat activation is due to a temperature-dependent shift of the activation curve, in analogy to other thermosensitive TRP channels3. Moreover, we show that increasing temperature between 15 and 35 °C markedly enhances the gustatory nerve response to sweet compounds in wild-type but not in Trpm5 knockout mice. The strong temperature sensitivity of TRPM5 may underlie known effects of temperature on perceived taste in humans4,5,6, including enhanced sweetness perception at high temperatures and ‘thermal taste’, the phenomenon whereby heating or cooling of the tongue evoke sensations of taste in the absence of tastants7.

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Figure 1: Heat activation of TRPM5.
Figure 2: Temperature dependence of TRPM5 in a high intracellular Ca 2+ concentration.
Figure 3: Comparison of the properties of TRPM8, TRPV1, TRPM4 and TRPM5.
Figure 4: Temperature dependence of chorda tympani nerve responses of wild-type and Trpm5 knockout mice.

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We thank V. Flockerzi, R. Vennekens and U. Wissenbach for the TRPM4 clone; N. Ullrich, G. Owsianik and F. Mahieu for discussions; and R. Yoshida, A. Janssens and J. Prenen for technical assistance. This work was supported by grants from the Human Frontiers Science Program, the Belgian Federal Government (Interuniversity Poles of Attraction Program, Prime Ministers Office), the Flemish Government and the Onderzoeksraad KU Leuven, and the NIH (to R.F.M.) and by a Grant-in-Aid for scientific research from the Japan Society for the Promotion of Science (to Y.N. and to N.S.).

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Correspondence to Karel Talavera.

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R.F.M. has a personal financial interest in the form of stock ownership in the Linguagen company, receives consulting fees from the Linguagen company, and is an inventor on patents and patent applications which have been licensed to the Linguagen company.

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Supplementary Notes

This file contains Supplementary Figures 1–3 and their legends, and Supplementary Methods (Modelling the gating of TRPM4 and TRPM5). (DOC 2208 kb)

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Talavera, K., Yasumatsu, K., Voets, T. et al. Heat activation of TRPM5 underlies thermal sensitivity of sweet taste. Nature 438, 1022–1025 (2005).

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