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CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes

Nature volume 495, pages 223–226 (2013)Cite this article

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Abstract

Recognition of sweet, bitter and umami tastes requires the non-vesicular release from taste bud cells of ATP, which acts as a neurotransmitter to activate afferent neural gustatory pathways1. However, how ATP is released to fulfil this function is not fully understood. Here we show that calcium homeostasis modulator 1 (CALHM1), a voltage-gated ion channel2,3, is indispensable for taste-stimuli-evoked ATP release from sweet-, bitter- and umami-sensing taste bud cells. Calhm1 knockout mice have severely impaired perceptions of sweet, bitter and umami compounds, whereas their recognition of sour and salty tastes remains mostly normal. Calhm1 deficiency affects taste perception without interfering with taste cell development or integrity. CALHM1 is expressed specifically in sweet/bitter/umami-sensing type II taste bud cells. Its heterologous expression induces a novel ATP permeability that releases ATP from cells in response to manipulations that activate the CALHM1 ion channel. Knockout of Calhm1 strongly reduces voltage-gated currents in type II cells and taste-evoked ATP release from taste buds without affecting the excitability of taste cells by taste stimuli. Thus, CALHM1 is a voltage-gated ATP-release channel required for sweet, bitter and umami taste perception.

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Figure 1: CALHM1 is selectively expressed in type II taste bud cells.
Figure 2: CALHM1 is essential for sweet, bitter and umami taste perception.
Figure 3: CALHM1 mediates ATP release.
Figure 4: CALHM1 is required for taste-evoked ATP release from taste cells.

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Acknowledgements

This work was supported by a KeySpan award to P.M., several US NIH grants (GM56328, MH059937, NS072775 to J.K.F.; DC10393 to M.G.T.; EY13624 to M.M.C.; R03DC011143 to I.M.; Core Grant P30 EY001583 to the University of Pennsylvania; Core Grant P30DC011735 to the Monell Chemical Senses Center) and the University of Minnesota’s Undergraduate Research Opportunities Program to S.L. and M.A. A.T. and M.O. are JSPS Fellows. We thank R. F. Margolskee for the TRPM5–GFP mice and Y. Ninomiya for comments on the manuscript.

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Author notes

  1. Ang Li

    Present address: Present address: Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.,

  2. Akiyuki Taruno and Valérie Vingtdeux: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Physiology, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Akiyuki Taruno, Zhongming Ma, Ang Li, Mortimer M. Civan & J. Kevin Foskett

  2. Litwin-Zucker Research Center for the Study of Alzheimer’s Disease, The Feinstein Institute for Medical Research, Manhasset, 11030, New York, USA

    Valérie Vingtdeux, Leslie Adrien, Haitian Zhao, Jeremy Koppel, Peter Davies & Philippe Marambaud

  3. Monell Chemical Senses Center, Philadelphia, 19104, Pennsylvania, USA

    Makoto Ohmoto, Ichiro Matsumoto & Michael G. Tordoff

  4. Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, 33136, Florida, USA

    Gennady Dvoryanchikov & Nirupa Chaudhari

  5. Department of Biomedical Sciences, Medical School, University of Minnesota Duluth, Duluth, 55812, Minnesota, USA

    Sze Leung, Maria Abernethy & Göran Hellekant

  6. Department of Pathology, Albert Einstein College of Medicine, Bronx, 10461, New York, USA

    Peter Davies

  7. Department of Medicine, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Mortimer M. Civan

  8. Program in Neurosciences, Miller School of Medicine, University of Miami, Miami, 33136, Florida, USA

    Nirupa Chaudhari

  9. Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    J. Kevin Foskett

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Contributions

A.T., V.V., A.L., Z.M., M.O., I.M., H.Z., L.A., S.L., M.A., G.H., G.D. and N.C. designed and performed experiments. P.M. and V.V. generated the Calhm1 knockout mice. J.K. and P.D. designed experiments. M.G.T., M.M.C., P.M. and J.K.F. designed experiments and helped with data interpretation. A.T., J.K.F. and P.M. wrote the manuscript.

Corresponding authors

Correspondence to Philippe Marambaud or J. Kevin Foskett.

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Taruno, A., Vingtdeux, V., Ohmoto, M. et al. CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes. Nature 495, 223–226 (2013). https://doi.org/10.1038/nature11906

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