title: CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes.
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.
authors: Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors: Akiyuki
authors: A
authors: Taruno
authors: Valérie
authors: V
authors: Vingtdeux
authors: Makoto
authors: M
authors: Ohmoto
authors: Zhongming
authors: Z
authors: Ma
authors: Gennady
authors: G
authors: Dvoryanchikov
authors: Ang
authors: A
authors: Li
authors: Leslie
authors: L
authors: Adrien
authors: Haitian
authors: H
authors: Zhao
authors: Sze
authors: S
authors: Leung
authors: Maria
authors: M
authors: Abernethy
authors: Jeremy
authors: J
authors: Koppel
authors: Peter
authors: P
authors: Davies
authors: Mortimer M
authors: MM
authors: Civan
authors: Nirupa
authors: N
authors: Chaudhari
authors: Ichiro
authors: I
authors: Matsumoto
authors: Göran
authors: G
authors: Hellekant
authors: Michael G
authors: MG
authors: Tordoff
authors: Philippe
authors: P
authors: Marambaud
authors: J Kevin
authors: JK
authors: Foskett
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D015640:Ion Channel Gating; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011983:Receptors, Purinergic / Q000378:metabolism; D059010:Single-Cell Analysis; D009435:Synaptic Transmission; D013649:Taste / Q000235:genetics / Q000502:physiology*; D013650:Taste Buds / Q000166:cytology / Q000378:metabolism
chemical_list: C530077:CALHM1 protein, human; C575356:CALHM1 protein, mouse; D015220:Calcium Channels; D008562:Membrane Glycoproteins; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate