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

Akiyuki Taruno; Valérie Vingtdeux; Makoto Ohmoto; Zhongming Ma; Gennady Dvoryanchikov; Ang Li; Leslie Adrien; Haitian Zhao; Sze Leung; Maria Abernethy; Jeremy Koppel; Peter Davies; Mortimer M. Civan; Nirupa Chaudhari; Ichiro Matsumoto; Goran B Hellekant; Michael G. Tordoff; Philippe Marambaud; J. Kevin Foskett

doi:10.1038/nature11906

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

Akiyuki Taruno, Valérie Vingtdeux, Makoto Ohmoto, Zhongming Ma, Gennady Dvoryanchikov, Ang Li, Leslie Adrien, Haitian Zhao, Sze Leung, Maria Abernethy, Jeremy Koppel, Peter Davies, Mortimer M. Civan, Nirupa Chaudhari, Ichiro Matsumoto, Goran B Hellekant, Michael G. Tordoff, Philippe Marambaud, J. Kevin Foskett

Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

368 Scopus citations

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 pathways. 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 channel, 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.

Original language	English (US)
Pages (from-to)	223-226
Number of pages	4
Journal	Nature
Volume	495
Issue number	7440
DOIs	https://doi.org/10.1038/nature11906
State	Published - Mar 14 2013

Bibliographical note

Funding Information:
Acknowledgements This work was supported by a KeySpan award to P.M., several US NIH grants (GM56328, MH059937, NS072775 to J.K.F.; DC10393 toM.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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Taruno, A., Vingtdeux, V., Ohmoto, M., Ma, Z., Dvoryanchikov, G., Li, A., Adrien, L., Zhao, H., Leung, S., Abernethy, M., Koppel, J., Davies, P., Civan, M. M., Chaudhari, N., Matsumoto, I., Hellekant, G. B., Tordoff, M. G., Marambaud, P., & Foskett, J. K. (2013). CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes. Nature, 495(7440), 223-226. https://doi.org/10.1038/nature11906

Taruno, A, Vingtdeux, V, Ohmoto, M, Ma, Z, Dvoryanchikov, G, Li, A, Adrien, L, Zhao, H, Leung, S, Abernethy, M, Koppel, J, Davies, P, Civan, MM, Chaudhari, N, Matsumoto, I, Hellekant, GB, Tordoff, MG, Marambaud, P & Foskett, JK 2013, 'CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes', Nature, vol. 495, no. 7440, pp. 223-226. https://doi.org/10.1038/nature11906

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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 pathways. 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 channel, 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.",

author = "Akiyuki Taruno and Val{\'e}rie Vingtdeux and Makoto Ohmoto and Zhongming Ma and Gennady Dvoryanchikov and Ang Li and Leslie Adrien and Haitian Zhao and Sze Leung and Maria Abernethy and Jeremy Koppel and Peter Davies and Civan, {Mortimer M.} and Nirupa Chaudhari and Ichiro Matsumoto and Hellekant, {Goran B} and Tordoff, {Michael G.} and Philippe Marambaud and Foskett, {J. Kevin}",

note = "Funding Information: Acknowledgements This work was supported by a KeySpan award to P.M., several US NIH grants (GM56328, MH059937, NS072775 to J.K.F.; DC10393 toM.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{\textquoteright}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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AU - Dvoryanchikov, Gennady

AU - Li, Ang

AU - Adrien, Leslie

AU - Zhao, Haitian

AU - Leung, Sze

AU - Abernethy, Maria

AU - Koppel, Jeremy

AU - Davies, Peter

AU - Civan, Mortimer M.

AU - Chaudhari, Nirupa

AU - Matsumoto, Ichiro

AU - Hellekant, Goran B

AU - Tordoff, Michael G.

AU - Marambaud, Philippe

AU - Foskett, J. Kevin

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N2 - 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 pathways. 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 channel, 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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CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes

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