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



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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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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Authors and Affiliations



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.

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Correspondence to Philippe Marambaud or J. Kevin Foskett.

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The authors declare no competing financial interests.

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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).

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