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  • 1
    Publication Date: 2013-03-08
    Description: 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.〈br /〉〈br /〉〈a href="" target="_blank"〉〈img src="" border="0"〉〈/a〉   〈a href="" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taruno, Akiyuki -- Vingtdeux, Valerie -- Ohmoto, Makoto -- Ma, Zhongming -- Dvoryanchikov, Gennady -- Li, Ang -- Adrien, Leslie -- Zhao, Haitian -- Leung, Sze -- Abernethy, Maria -- Koppel, Jeremy -- Davies, Peter -- Civan, Mortimer M -- Chaudhari, Nirupa -- Matsumoto, Ichiro -- Hellekant, Goran -- Tordoff, Michael G -- Marambaud, Philippe -- Foskett, J Kevin -- DC10393/DC/NIDCD NIH HHS/ -- EY13624/EY/NEI NIH HHS/ -- GM56328/GM/NIGMS NIH HHS/ -- MH059937/MH/NIMH NIH HHS/ -- NS072775/NS/NINDS NIH HHS/ -- P30 DC011735/DC/NIDCD NIH HHS/ -- P30 EY001583/EY/NEI NIH HHS/ -- P30DC011735/DC/NIDCD NIH HHS/ -- R01 DC006308/DC/NIDCD NIH HHS/ -- R01 DC010393/DC/NIDCD NIH HHS/ -- R01 EY013624/EY/NEI NIH HHS/ -- R01 MH059937/MH/NIMH NIH HHS/ -- R03 DC011143/DC/NIDCD NIH HHS/ -- R03DC011143/DC/NIDCD NIH HHS/ -- R21 NS072775/NS/NINDS NIH HHS/ -- R37 GM056328/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 Mar 14;495(7440):223-6. doi: 10.1038/nature11906. Epub 2013 Mar 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Calcium Channels/deficiency/genetics/*metabolism ; Female ; HeLa Cells ; Humans ; Ion Channel Gating ; Male ; Membrane Glycoproteins/genetics/metabolism ; Mice ; Mice, Knockout ; Receptors, Purinergic/metabolism ; Single-Cell Analysis ; *Synaptic Transmission ; Taste/genetics/*physiology ; Taste Buds/cytology/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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