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PLOS ONE  2009 

Sour Ageusia in Two Individuals Implicates Ion Channels of the ASIC and PKD Families in Human Sour Taste Perception at the Anterior Tongue

DOI: 10.1371/journal.pone.0007347

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Background The perception of sour taste in humans is incompletely understood at the receptor cell level. We report here on two patients with an acquired sour ageusia. Each patient was unresponsive to sour stimuli, but both showed normal responses to bitter, sweet, and salty stimuli. Methods and Findings Lingual fungiform papillae, containing taste cells, were obtained by biopsy from the two patients, and from three sour-normal individuals, and analyzed by RT-PCR. The following transcripts were undetectable in the patients, even after 50 cycles of amplification, but readily detectable in the sour-normal subjects: acid sensing ion channels (ASICs) 1a, 1β, 2a, 2b, and 3; and polycystic kidney disease (PKD) channels PKD1L3 and PKD2L1. Patients and sour-normals expressed the taste-related phospholipase C-β2, the δ-subunit of epithelial sodium channel (ENaC) and the bitter receptor T2R14, as well as β-actin. Genomic analysis of one patient, using buccal tissue, did not show absence of the genes for ASIC1a and PKD2L1. Immunohistochemistry of fungiform papillae from sour-normal subjects revealed labeling of taste bud cells by antibodies to ASICs 1a and 1β, PKD2L1, phospholipase C-β2, and δ-ENaC. An antibody to PKD1L3 labeled tissue outside taste bud cells. Conclusions These data suggest a role for ASICs and PKDs in human sour perception. This is the first report of sour ageusia in humans, and the very existence of such individuals (“natural knockouts”) suggests a cell lineage for sour that is independent of the other taste modalities.


[1]  Bradley RM (1971) Tongue topography. In: Beidler L, editor. Handbook of Sensory Physiology, Volume IV, Chemical Senses, Part 2. Berlin, Heidelberg, New York: Springer-Verlag. pp. 1–30.
[2]  DeFazio RA, Dvoryanchikov G, Maruyama Y, Kim JW, Pereira E, et al. (2006) Separate populations of receptor cells and presynaptic cells in mouse taste buds. J Neurosci 26: 3971–3980.
[3]  Chandrashekar J, Hoon MA, Ryba NJP, Zuker CS (2006) The receptors and cells for mammalian taste. Nature 444: 288–294.
[4]  Makhlouf GM, Blum AL (1972) Kinetics of the taste response to chemical stimulation: a theory of acid taste in man. Gastroenterology 63: 67–75.
[5]  Norris MB, Noble AC, Pangborn RM (1984) Human saliva and taste responses to acids varying in anions, titratable acidity, and pH. Physiol Behav 32: 237–244.
[6]  DeSimone JA, Lyall V, Heck GL, Feldman GM (2001) Acid detection by taste receptor cells. Respir Physiol 129: 231–245.
[7]  Da Conceicao Neta ER, Johanningsmeier SD, McFeeters RF (2007) The chemistry and physiology of sour taste – a review. J Food Sci 72: R33–R38.
[8]  Waldmann R, Champigny G, Bassilana F, Heurteaux C, Lazdunski M (1997) A proton-gated cation channel involved in acid-sensing. Nature 386: 173–177.
[9]  Waldmann R, Lazdunski M (1998) H(+)-gated cation channels: neuronal acid sensors in the NaC/DEG family of ion channels. Curr Opin Neurobiol 8: 418–424.
[10]  Kress M, Waldmann R (2006) Acid sensing ionic channels. Curr Topics Membranes 57: 241–276.
[11]  Lingueglia E (2007) Acid-sensing ion channels in sensory perception. J Biol Chem 282: 17325–17329.
[12]  Krishtal O (2003) The ASICs: signaling molecules? Modulators? Trends Neurosci 26: 477–483.
[13]  Ugawa S, Minami Y, Guo W, Saishin Y, Takatsuji K, et al. (1998) Receptor that leaves a sour taste in the mouth. Nature 395: 555–556.
[14]  Liu L, Simon SA (2001) Acidic stimuli activates two distinct pathways in taste receptor cells from rat fungiform papillae. Brain Res 923: 58–70.
[15]  Huque T, Nguyen ND, Puchalski RB, Spielman AI, Breslin PA, et al. (2001) Cloning and expression of ASIC1 from human fungiform papillae. Chem Senses 26: 1060 (Abstract).
[16]  LopezJimenez ND, Cavenagh MM, Sainz E, Cruz-Ithier MA, Battey JF, et al. (2006) Two members of the TRPP family of ion channels, Pkd1l3 and Pkd2l1, are co-expressed in a subset of taste receptor cells. J Neurochem 98: 68–77.
[17]  Ishimaru Y, Inada H, Kubota M, Zhuang H, Tominaga M, et al. (2006) Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor. Proc Natl Acad Sci USA 103: 12569–12574.
[18]  Huang AL, Chen X, Hoon MA, Chandrashekar J, Guo W, et al. (2006) The cells and logic for mammalian sour taste detection. Nature 442: 934–938.
[19]  Gilbertson TA, Avenet P, Kinnamon SC, Roper SD (1992) Proton currents through amiloride-sensitive Na channels in hamster taste cells. Role in acid transduction. J Gen Physiol 100: 803–824.
[20]  Yamamura H, Ugawa S, Ueda T, Nagao M, Shimada S (2004) Protons activate the delta-subunit of the epithelial Na+ channel in humans. J Biol Chem 279: 12529–12534.
[21]  Hille B (1992) Ion Channels of Excitable Membranes. Sunderland, MA: Sinauer. 814 p.
[22]  Putnam RW, Filosa JA, Ritucci NA (2004) Cellular mechanisms involved in CO2 and acid signaling in chemosensitive neurons. Am J Physiol Cell Physiol 287: C1493–1526.
[23]  Holzer P (2007) Taste receptors in the gastrointestinal tract. V. Acid sensing in the gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol 292: G669–705.
[24]  Cao J, Huque T, Spielman AI, Breslin PAS, Brand JG (2002) Polymorphisms in an acid sensing ion channel (hfpASIC1) in human fungiform papillae. Proc Assoc of Chemoreception Sciences XXIV A76 (Abstract).
[25]  Huque T, Lischka F, Spielman AI, Bayley DL, Cao J, et al. (2003) Expression of acid sensing ion channels in isolated human taste receptor cells. Proc Assoc for Chemoreception Sciences XXV A287 (Abstract).
[26]  Pribitkin E, Rosenthal MD, Cowart BJ (2003) Prevalence and causes of severe taste loss in a chemosensory clinic population. Ann Otol Rhinol Laryngol 112: 971–978.
[27]  Schiffman SS, Zervakis J (2002) Taste and smell perception in the elderly: effect of medications and disease. Adv Food Nutr Res 44: 247–346.
[28]  Weiffenbach JM, Baum BJ, Burghauser R (1982) Taste thresholds: quality specific variation with human aging. J Gerontol 37: 372–377.
[29]  Physicians' Desk Reference (2007) Montvale, NJ: Thomson Reuters. 3000 p. Vol. 61.
[30]  Uhr M, Grauer MT, Yassouridis A, Ebinger M (2007) Blood-brain barrier penetration and pharmacokinetics of amitriptyline and its metabolites in p-glycoprotein (abcb1ab) knock-out mice and controls. J Psychiatr Res 41: 179–188.
[31]  Holtzman CW, Wiggins BS, Spinier SA (2006) Role of p-glycoprotein in statin drug interactions. Pharmacotherapy 26: 1601–1607.
[32]  Farbman AI, Gonzales F, Chuah MI (1988) The effect of amitriptyline on growth of olfactory and cerebral neurons in vitro. Brain Res 457: 282–286.
[33]  Schiffman SS (2007) Critical illness and changes in sensory perception. Proc Nutr Soc 66: 331–345.
[34]  Wang H, Zhou M, Brand J, Huang L (2007) Inflammation activates the interferon signaling pathways in taste bud cells. J Neurosci 27: 10703–10713.
[35]  Nakazato Y, Ito Y, Naito S, Tamura N, Shimazu K (2008) Dysgeusia limited to sweet taste in myasthenia gravis. Intern Med 47: 877–878.
[36]  Huque T, Wysocki L, Bayley DL, Breslin PA, Spielman AI, et al. (2002) Expression of epithelial sodium channels in human fungiform papillae. Proc Assoc of Chemoreception Sciences XXIV A87 (Abstract).
[37]  Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, et al. (2003) Coding of sweet, bitter and umami tastes: different receptor cells sharing similar signaling pathways. Cell 112: 293–301.
[38]  Behrens M, Brockhoff A, Kuhn C, Bufe B, Winnig M, et al. (2004) The human taste receptor hTAS2R14 responds to a variety of different bitter compounds. Biochem Biophys Res Commun 319: 479–485.
[39]  St?hler F, Riedel K, Demgensky S, Neumann K, Dunkel A, et al. (2008) A role of the epithelial sodium channel in human salt taste transduction? Chem Percept 1: 78–90.
[40]  Shin Y-K, Martin B, Golden E, Dotson C, Maudsley S, et al. (2008) Modulation of taste sensitivity by GLP-1 signaling in taste buds. Proc International Symposium on Olfaction and Taste XV A415 (Abstract).
[41]  Sandick B, Cardello AV (1981) Taste profiles from single circumvallate papillae: comparison with fungiform profiles. Chem Senses 6: 197–214.
[42]  Cardello AV (1979) Taste quality changes as a function of salt concentration in single human taste papillae. Chem Senses 4: 1–13.
[43]  Tomchik SM, Berg S, Kim JW, Chaudhari N, Roper SD (2007) Breadth of tuning and taste coding in mammalian taste buds. J Neurosci 27: 10840–10848.
[44]  Stone LM, Tan S-S, Tam PPL, Finger TE (2002) Analysis of cell lineage relationships in taste buds. J Neurosci 22: 4522–4529.
[45]  Richter TA, Dvoryanchikov GA, Chaudhari N, Roper SD (2004) Acid sensitive two-pore domain potassium (K2P) channels in mouse taste buds. J Neurophysiol 92: 1928–1936.
[46]  Ugawa S, Ueda T, Takahashi E, Hirabayashi Y, Yoneda T, et al. (2003) Amiloride-insensitive currents of the acid sensing ion channel 2a (ASIC2a)/ASIC2b heteromeric sour-taste receptor channel. J Neurosci 23: 3616–3622.
[47]  Bandell M, Macpherson LJ, Patapoutian A (2007) From chills to chilis: mechanisms for thermosensation and chemesthesis via thermo TRPs. Curr Op Neurobiol 17: 490–497.
[48]  Bachmanov AA, Tordoff MG, Beauchamp GK (1996) Ethanol consumption and taste preferences in C57BL/6ByJ and 129/J mice. Alcohol Clin Exp Res 20: 201–206.
[49]  Richter TA, Dvoryanchikov GA, Roper SD, Chaudhari N (2004) Acid-sensing ion channel-2 is not necessary for sour taste in mice. J Neurosci 24: 4088–4091.
[50]  Nelson TM, LopezJimenez ND, Tessarollo L, Inoue M, McCaughey SA, et al. (2008) Taste function in PKD1L3 knockout mice. Proc International Symposium on Olfaction and Taste XV A345 (Abstract).
[51]  Cowart BJ (1989) Relationships between taste and smell across the life-span. Ann NY Acad Sci 561: 39–55.
[52]  Spielman AI, Brand JG (1995) Collection of taste tissue from mammals. In: Spielman AI, Brand JG, editors. Experimental Cell Biology of Taste and Olfaction: Current Techniques and Protocols. Boca Raton: CRC Press. pp. 25–32.
[53]  Iwayama T, Nada O (1967) Histochemically demonstrable ATPase activity in the taste buds of the rat. Exptl Cell Res 46: 607–608.


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