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.
SourceAvailable from: Jonathan Beckel[Show abstract] [Hide abstract]
ABSTRACT: ATP is released from the bladder epithelium, also termed the urothelium, in response to mechanical or chemical stimuli. While numerous studies have described the contribution of this release to the development of various bladder disorders, little information exists regarding the mechanisms of release. In the present study, we examined the role of pannexin channels in mechanically-induced ATP release from the urothelium. PCR confirmed the presence of pannexin 1 and 2 mRNA in rat urothelial tissue, while immunofluorescence experiments localized pannexin 1 to all three layers of the urothelium. During continuous bladder cystometry in anesthetized rats, inhibition of pannexin 1 channels using carbenoxolone (CBX) or Brilliant Blue FCF (BB-FCF) (1–100μM, intravesically), or by using intravesical siRNA, increased the interval between voiding contractions. Intravenous administration of BB-FCF (1–100 μg/kg) did not alter bladder activity. CBX or BB-FCF, (100μM intravesically) also decreased basal ATP concentrations in the perfusate from non-distended bladders and inhibited increases in ATP concentrations in response to bladder distension (15 and 30 cm H20 pressure). Intravesical perfusion of the ATP diphosphohydrolase apyrase (2 U/ml), or the ATPase inhibitor ARL67156 (10μM) increased or decreased reflex bladder activity, respectively. Intravesical instillation of bacterial lipopolysaccharides (LPS, E. coli 055:B5, 100 μg/ml) increased ATP concentrations in the bladder perfusate as well as increased voiding frequency; effects that were suppressed by BB-FCF. These data indicate that pannexin channels contribute to distention- or LPS-evoked ATP release into the lumen of the bladder and that luminal release can modulate voiding function.This article is protected by copyright. All rights reservedThe Journal of Physiology 01/2015; DOI:10.1113/jphysiol.2014.283119 · 4.38 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Laboratory rats and mice prefer some concentrations of tri- and tetrasodium pyrophosphate (Na3HP2O7 and Na4P2O7) to water, but how they detect pyrophosphates is unknown. Here, we assessed whether T1R3 is involved. We found that relative to wild-type littermate controls, Tas1r3 knockout mice had stronger preferences for 5.6-56mM Na3HP2O7 in 2-bottle choice tests, and they licked more 17.8-56mM Na3HP2O7 in brief-access tests. We hypothesize that pyrophosphate taste in the intact mouse involves 2 receptors: T1R3 to produce a hedonically negative signal and an unknown G protein-coupled receptor to produce a hedonically positive signal; in Tas1r3 knockout mice, the hedonically negative signal produced by T1R3 is absent, leading to a heightened avidity for pyrophosphate. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.Chemical Senses 12/2014; 40(1). DOI:10.1093/chemse/bju059 · 3.28 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The sense of taste facilitates the recognition of beneficial or potentially harmful food constituents prior to ingestion. For the detection of tastants, epithelial specializations in the oral cavity are equipped with taste receptor molecules that interact with sweet, umami (the taste of l-amino acids), salty, sour, and bitter-tasting substances. Over the past years, numerous tissues in addition to gustatory sensory tissue have been identified to express taste receptor molecules. These findings bear important implications for the roles taste receptors fulfill in vertebrates, which are currently envisioned much broader than thought previously. Taste receptive molecules are present in the brain, respiratory and gastrointestinal tracts, heart, male reproductive tissue, as well as other areas of the body just beginning to emerge. This review summarizes current knowledge on the occurrence and functional implications of taste receptive molecules outside the oral cavity.Topics in Medicinal Chemistry, 10/2014; Springer Berlin Heidelberg.