Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Heat activation of TRPM5 underlies thermal sensitivity of sweet taste

Abstract

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

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.

References

  1. 1

    Perez, C. A. et al. A transient receptor potential channel expressed in taste receptor cells. Nature Neurosci. 5, 1169–1176 (2002)

    CAS  Article  Google Scholar 

  2. 2

    Zhang, Y. et al. Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signalling pathways. Cell 112, 293–301 (2003)

    CAS  Article  Google Scholar 

  3. 3

    Voets, T. et al. The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels. Nature 430, 748–754 (2004)

    ADS  CAS  Article  Google Scholar 

  4. 4

    Bartoshuk, L. M., Rennert, K., Rodin, J. & Stevens, J. C. Effects of temperature on the perceived sweetness of sucrose. Physiol. Behav. 28, 905–910 (1982)

    CAS  Article  Google Scholar 

  5. 5

    Green, B. G. & Frankmann, S. P. The effect of cooling on the perception of carbohydrate and intensive sweeteners. Physiol. Behav. 43, 515–519 (1988)

    CAS  Article  Google Scholar 

  6. 6

    Green, B. G. & Frankmann, S. P. The effect of cooling the tongue on the perceived intensity of taste. Chem. Senses 12, 609–619 (1987)

    CAS  Article  Google Scholar 

  7. 7

    Cruz, A. & Green, B. G. Thermal stimulation of taste. Nature 403, 889–892 (2000)

    ADS  CAS  Article  Google Scholar 

  8. 8

    Clapham, D. E. TRP channels as cellular sensors. Nature 426, 517–524 (2003)

    ADS  CAS  Article  Google Scholar 

  9. 9

    Patapoutian, A., Peier, A. M., Story, G. M. & Viswanath, V. ThermoTRP channels and beyond: mechanisms of temperature sensation. Nature Rev. Neurosci. 4, 529–539 (2003)

    CAS  Article  Google Scholar 

  10. 10

    Patapoutian, A. TRP channels and thermosensation. Chem. Senses 30 (suppl. 1), i193–i194 (2005)

    CAS  Article  Google Scholar 

  11. 11

    Hille, B. in Ion Channels of Excitable Membranes (ed. Hille, B.) Ch. 11, 366 (Sinauer Associates, Sunderland, 2001)

    Google Scholar 

  12. 12

    Liu, D. & Liman, E. R. Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5. Proc. Natl Acad. Sci. USA 100, 15160–15165 (2003)

    ADS  CAS  Article  Google Scholar 

  13. 13

    Prawitt, D. et al. TRPM5 is a transient Ca2+-activated cation channel responding to rapid changes in [Ca2+]i . Proc. Natl Acad. Sci. USA 100, 15166–15171 (2003)

    ADS  CAS  Article  Google Scholar 

  14. 14

    Ullrich, N. D. et al. Comparison of functional properties of the Ca2+-activated cation channels TRPM4 and TRPM5 from mice. Cell Calcium 37, 267–278 (2005)

    CAS  Article  Google Scholar 

  15. 15

    Nilius, B. et al. Regulation of the Ca2+ sensitivity of the nonselective cation channel TRPM4. J. Biol. Chem. 280, 6423–6433 (2005)

    CAS  Article  Google Scholar 

  16. 16

    van Lunteren, E., Elmslie, K. S. & Jones, S. W. Effects of temperature on calcium current of bullfrog sympathetic neurons. J. Physiol. Lond. 466, 81–93 (1993)

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

    Tiwari, J. K. & Sikdar, S. K. Temperature-dependent conformational changes in a voltage-gated potassium channel. Eur. Biophys. J. 28, 338–345 (1999)

    CAS  Article  Google Scholar 

  18. 18

    Correa, A. M., Bezanilla, F. & Latorre, R. Gating kinetics of batrachotoxin-modified Na+ channels in the squid giant axon. Voltage and temperature effects. Biophys. J. 61, 1332–1352 (1992)

    CAS  Article  Google Scholar 

  19. 19

    Voets, T., Talavera, K., Owsianik, G. & Nilius, B. Sensing with TRP channels. Nature Chem. Biol. 1, 85–92 (2005)

    CAS  Article  Google Scholar 

  20. 20

    Talavera, K., Janssens, A., Klugbauer, N., Droogmans, G. & Nilius, B. Extracellular Ca2+ modulates the effects of protons on gating and conduction properties of the T-type Ca2+ channel α1G (CaV3.1). J. Gen. Physiol. 121, 511–528 (2003)

    CAS  Article  Google Scholar 

  21. 21

    Rong, M. et al. Signal transduction of umami taste: insights from knockout mice. Chem. Senses 30, i33–i34 (2005)

    CAS  Article  Google Scholar 

  22. 22

    Kawai, K., Sugimoto, K., Nakashima, K., Miura, H. & Ninomiya, Y. Leptin as a modulator of sweet taste sensitivities in mice. Proc. Natl Acad. Sci. USA 97, 11044–11049 (2000)

    ADS  CAS  Article  Google Scholar 

Download references

Acknowledgements

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.).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Karel Talavera.

Ethics declarations

Competing interests

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.

Supplementary information

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)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Talavera, K., Yasumatsu, K., Voets, T. et al. Heat activation of TRPM5 underlies thermal sensitivity of sweet taste. Nature 438, 1022–1025 (2005). https://doi.org/10.1038/nature04248

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing