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

1] Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA [2].
Nature (Impact Factor: 41.46). 03/2013; 495(7440). DOI: 10.1038/nature11906
Source: PubMed


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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    • "Type I cells express membrane-localized NTPDase2 (Entpd2), an ectoATPase that converts ATP to ADP. Type II cells use ATP as a neurotransmitter to signal to sensory nerves (Finger et al., 2005; Vandenbeuch et al., 2015), yet Type II cells lack presynaptic specializations; rather, Type II cells release ATP in a non-vesicular manner (Huang et al., 2007; Romanov et al., 2013, 2007), probably via CALMH1 ion channels (Taruno et al., 2013). Thus, NTPDase2- expressing Type I cells are likely to clear excess ATP released by Type II cells to ensure efficient neurotransmission (Bartel et al., 2006; Finger et al., 2005; Vandenbeuch et al., 2013). "
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    ABSTRACT: The sense of taste, or gustation, is mediated by taste buds, which are housed in specialized taste papillae found in a stereotyped pattern on the surface of the tongue. Each bud, regardless of its location, is a collection of ~100 cells that belong to at least five different functional classes, which transduce sweet, bitter, salt, sour and umami (the taste of glutamate) signals. Taste receptor cells harbor functional similarities to neurons but, like epithelial cells, are rapidly and continuously renewed throughout adult life. Here, I review recent advances in our understanding of how the pattern of taste buds is established in embryos and discuss the cellular and molecular mechanisms governing taste cell turnover. I also highlight how these findings aid our understanding of how and why many cancer therapies result in taste dysfunction.
    Development 11/2015; 142(21):3620-3629. DOI:10.1242/dev.120394 · 6.46 Impact Factor
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    • "Not a complete taste loss in the absence of Calhm1—suggesting multiple channels may be involved (Taruno et al. 2013) Panx1-KO mice detect taste stimuli like WT mice (Tordoff et al. this issue; Vandenbeuch et al. this issue) "
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    ABSTRACT: Studies over the last 8 years have identified 3 potential channels that appear to release ATP from Type II cells in response to taste stimuli. These studies have taken different methodological approaches but have all provided data supporting their candidate channel as the ATP release channel. These potential channels include Pannexin 1, Connexins (30 and/or 43), and most recently, the Calhm1 channel. Two papers in this issue of Chemical Senses provide compelling new evidence that Pannexin 1 is not the ATP release channel. Tordoff et al. did a thorough behavioral analysis of the Pannexin1 knock out mouse and found that these animals have the same behavioral responses as wild type mice for 7 different taste stimuli that were tested. Vandenbeuch et al. presented an equally thorough analysis of the gustatory nerve responses in the Pannexin1 knock out mouse and found no differences compared with controls. Thus when the role of Pannexin 1 is analyzed at the systems level, it is not required for normal taste perception. Further studies are needed to determine the role of this hemichannel in taste cells. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail:
    Chemical Senses 06/2015; 40(7). DOI:10.1093/chemse/bjv035 · 3.16 Impact Factor
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    • "The NG in KO mice showed no response to sweet, a slight response to umami, a much smaller response to bitter, but no significant difference in responses to salty and sour compounds. These data are similar to our results of CALHM1 KO in CT nerve recordings except in regard to the umami response (Taruno et al. 2013). "
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    ABSTRACT: Stimulation of Type II taste receptor cells (TRCs) with T1R taste receptors causes sweet or umami taste, whereas T2Rs elicit bitter taste. Type II TRCs contain the calcium channel, calcium homeostasis modulator protein 1 (CALHM1), which releases adenosine triphosphate (ATP) transmitter to taste fibers. We have previously demonstrated with chorda tympani nerve recordings and two-bottle preference (TBP) tests that mice with genetically deleted Calhm1 (knockout [KO]) have severely impaired perception of sweet, bitter, and umami compounds, whereas their sour and salty tasting ability is unaltered. Here, we present data from KO mice of effects on glossopharyngeal (NG) nerve responses, TBP, food intake, body weight, and life span. KO mice have no NG response to sweet and a suppressed response to bitter compared with control (wild-type [WT]) mice. KO mice showed some NG response to umami, suggesting that umami taste involves both CALHM1- and non-CALHM1-modulated signals. NG responses to sour and salty were not significantly different between KO and WT mice. Behavioral data conformed in general with the NG data. Adult KO mice consumed less food, weighed significantly less, and lived almost a year longer than WT mice. Taken together, these data demonstrate that sweet taste majorly influences food intake, body weight, and life span. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail:
    Chemical Senses 04/2015; 40(6). DOI:10.1093/chemse/bjv009 · 3.16 Impact Factor
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