Molecular and Cellular Mechanisms of Salt Taste

Literature Cited

1. 1.

   Chandrashekar J, Kuhn C, Oka Y, Yarmolinsky DA, Hummler E et al. 2010. The cells and peripheral representation of sodium taste in mice. Nature 464:297–301Demonstrates that dedicated taste cells mediate sodium taste with ENaC as a sensor molecule.
   [Google Scholar]
2. 2.

   Drewnowski A, Henderson SA, Driscoll A, Rolls BJ. 1996. Salt taste perceptions and preferences are unrelated to sodium consumption in healthy older adults. J. Am. Diet. Assoc. 96:471–74
   [Google Scholar]
3. 3.

   Duncan CJ. 1962. Salt preferences of birds and mammals. Physiol. Zool. 35:120–32
   [Google Scholar]
4. 4.

   Oka Y, Butnaru M, von Buchholtz L, Ryba NJ, Zuker CS 2013. High salt recruits aversive taste pathways. Nature 494:472–75Demonstrates a requirement for bitter and sour taste cells in high salt aversion.
   [Google Scholar]
5. 5.

   WHO (World Health Organ.) 2012. Guideline: sodium intake for adults and children WHO Geneva: https://www.who.int/publications/i/item/9789241504836
6. 6.

   Mozaffarian D, Fahimi S, Singh GM, Micha R, Khatibzadeh S et al. 2014. Global sodium consumption and death from cardiovascular causes. N. Engl. J. Med. 371:624–34
   [Google Scholar]
7. 7.

   Turner HN, Liman ER. 2022. The cellular and molecular basis of sour taste. Annu. Rev. Physiol. 84:41–58
   [Google Scholar]
8. 8.

   Heck GL, Mierson S, DeSimone JA. 1984. Salt taste transduction occurs through an amiloride-sensitive sodium transport pathway. Science 223:403–5Discovered the existence of an Na⁺-selective, amiloride-sensitive salt taste (sodium taste) transduction in rats.
   [Google Scholar]
9. 9.

   Spector AC, Guagliardo NA, St. John SJ 1996. Amiloride disrupts NaCl versus KCl discrimination performance: implications for salt taste coding in rats. J. Neurosci. 16:8115–22
   [Google Scholar]
10. 10.

    Beidler LM. 1954. A theory of taste stimulation. J. Gen. Physiol. 38:133–39
    [Google Scholar]
11. 11.

    DeSimone JA, Heck GL, DeSimone SK. 1981. Active ion transport in dog tongue: a possible role in taste. Science 214:1039–41
    [Google Scholar]
12. 12.

    DeSimone JA, Heck GL, Mierson S, Desimone SK. 1984. The active ion transport properties of canine lingual epithelia in vitro. Implications for gustatory transduction. J. Gen. Physiol. 83:633–56
    [Google Scholar]
13. 13.

    Canessa CM, Schild L, Buell G, Thorens B, Gautschi I et al. 1994. Amiloride-sensitive epithelial Na⁺ channel is made of three homologous subunits. Nature 367:463–67
    [Google Scholar]
14. 14.

    Noreng S, Bharadwaj A, Posert R, Yoshioka C, Baconguis I 2018. Structure of the human epithelial sodium channel by cryo-electron microscopy. eLife 7:e39340
    [Google Scholar]
15. 15.

    Schiffman SS, Lockhead E, Maes FW. 1983. Amiloride reduces the taste intensity of Na⁺ and Li⁺ salts and sweeteners. PNAS 80:6136–40
    [Google Scholar]
16. 16.

    Halpern BP. 1998. Amiloride and vertebrate gustatory responses to NaCl. Neurosci. Biobehav. Rev. 23:5–47
    [Google Scholar]
17. 17.

    Avenet P, Lindemann B. 1988. Amiloride-blockable sodium currents in isolated taste receptor cells. J. Membr. Biol. 105:245–55
    [Google Scholar]
18. 18.

    Bigiani A, Cuoghi V. 2007. Localization of amiloride-sensitive sodium current and voltage-gated calcium currents in rat fungiform taste cells. J. Neurophysiol. 98:2483–87
    [Google Scholar]
19. 19.

    Doolin RE, Gilbertson TA. 1996. Distribution and characterization of functional amiloride-sensitive sodium channels in rat tongue. J. Gen. Physiol. 107:545–54
    [Google Scholar]
20. 20.

    Miyamoto T, Miyazaki T, Okada Y, Sato T. 1996. Whole-cell recording from non-dissociated taste cells in mouse taste bud. J. Neurosci. Methods 64:245–52
    [Google Scholar]
21. 21.

    Kretz O, Barbry P, Bock R, Lindemann B. 1999. Differential expression of RNA and protein of the three pore-forming subunits of the amiloride-sensitive epithelial sodium channel in taste buds of the rat. J. Histochem. Cytochem. 47:51–64
    [Google Scholar]
22. 22.

    Ninomiya Y. 1998. Reinnervation of cross-regenerated gustatory nerve fibers into amiloride-sensitive and amiloride-insensitive taste receptor cells. PNAS 95:5347–50
    [Google Scholar]
23. 23.

    Nomura K, Nakanishi M, Ishidate F, Iwata K, Taruno A. 2020. All-electrical Ca²⁺-independent signal transduction mediates attractive sodium taste in taste buds. Neuron 106:816–29.e6Identifies the cells, signal transduction, and neurotransmission mechanisms underlying sodium taste in mice.
    [Google Scholar]
24. 24.

    Lossow K, Hermans-Borgmeyer I, Meyerhof W, Behrens M. 2020. Segregated expression of ENaC subunits in taste cells. Chem. Senses 45:235–48
    [Google Scholar]
25. 25.

    Vandenbeuch A, Clapp TR, Kinnamon SC. 2008. Amiloride-sensitive channels in type I fungiform taste cells in mouse. BMC Neurosci. 9:1
    [Google Scholar]
26. 26.

    Ma Z, Taruno A, Ohmoto M, Jyotaki M, Lim JC et al. 2018. CALHM3 is essential for rapid ion channel-mediated purinergic neurotransmission of GPCR-mediated tastes. Neuron 98:547–61.e10Discovered CALHM1/CALHM3 as the bona fide neurotransmitter-release channel complex in type II cells of mice.
    [Google Scholar]
27. 27.

    Taruno A, Vingtdeux V, Ohmoto M, Ma Z, Dvoryanchikov G et al. 2013. CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes. Nature 495:223–26
    [Google Scholar]
28. 28.

    Bigiani A. 2017. Calcium homeostasis modulator 1-like currents in rat fungiform taste cells expressing amiloride-sensitive sodium currents. Chem. Senses 42:343–59
    [Google Scholar]
29. 29.

    Tordoff MG, Ellis HT, Aleman TR, Downing A, Marambaud P et al. 2014. Salty taste deficits in CALHM1 knockout mice. Chem. Senses 39:515–28
    [Google Scholar]
30. 30.

    Matsumoto I, Ohmoto M, Narukawa M, Yoshihara Y, Abe K 2011. Skn-1a (Pou2f3) specifies taste receptor cell lineage. Nat. Neurosci. 14:685–87
    [Google Scholar]
31. 31.

    Ohmoto M, Jyotaki M, Foskett JK, Matsumoto I. 2020. Sodium-taste cells require Skn-1a for generation and share molecular features with sweet, umami, and bitter taste cells. eNeuro 7: ENEURO.0385–20.2020
    [Google Scholar]
32. 32.

    Yang R, Dzowo YK, Wilson CE, Russell RL, Kidd GJ et al. 2020. Three-dimensional reconstructions of mouse circumvallate taste buds using serial blockface scanning electron microscopy: I. Cell types and the apical region of the taste bud. J. Comp. Neurol. 528:756–71
    [Google Scholar]
33. 33.

    Romanov RA, Kolesnikov SS. 2006. Electrophysiologically identified subpopulations of taste bud cells. Neurosci. Lett. 395:249–54
    [Google Scholar]
34. 34.

    Taruno A, Nomura K, Kusakizako T, Ma Z, Nureki O, Foskett JK. 2021. Taste transduction and channel synapses in taste buds. Pflügers Arch. 473:3–13
    [Google Scholar]
35. 35.

    Romanov RA, Rogachevskaja OA, Bystrova MF, Jiang P, Margolskee RF, Kolesnikov SS. 2007. Afferent neurotransmission mediated by hemichannels in mammalian taste cells. EMBO J. 26:657–67
    [Google Scholar]
36. 36.

    Huang YJ, Maruyama Y, Dvoryanchikov G, Pereira E, Chaudhari N, Roper SD. 2007. The role of pannexin 1 hemichannels in ATP release and cell-cell communication in mouse taste buds. PNAS 104:6436–41
    [Google Scholar]
37. 37.

    Finger TE, Danilova V, Barrows J, Bartel DL, Vigers AJ et al. 2005. ATP signaling is crucial for communication from taste buds to gustatory nerves. Science 310:1495–99
    [Google Scholar]
38. 38.

    Bo X, Alavi A, Xiang Z, Oglesby I, Ford A, Burnstock G. 1999. Localization of ATP-gated P2X2 and P2X3 receptor immunoreactive nerves in rat taste buds. Neuroreport 10:1107–11
    [Google Scholar]
39. 39.

    Vandenbeuch A, Anderson CB, Parnes J, Enjyoji K, Robson SC et al. 2013. Role of the ectonucleotidase NTPDase2 in taste bud function. PNAS 110:14789–94
    [Google Scholar]
40. 40.

    Dreses-Werringloer U, Lambert JC, Vingtdeux V, Zhao H, Vais H et al. 2008. A polymorphism in CALHM1 influences Ca²⁺ homeostasis, Aβ levels, and Alzheimer's disease risk. Cell 133:1149–61
    [Google Scholar]
41. 41.

    Ma Z, Siebert AP, Cheung KH, Lee RJ, Johnson B et al. 2012. Calcium homeostasis modulator 1 (CALHM1) is the pore-forming subunit of an ion channel that mediates extracellular Ca²⁺ regulation of neuronal excitability. PNAS 109:E1963–71
    [Google Scholar]
42. 42.

    Siebert AP, Ma Z, Grevet JD, Demuro A, Parker I, Foskett JK. 2013. Structural and functional similarities of calcium homeostasis modulator 1 (CALHM1) ion channel with connexins, pannexins, and innexins. J. Biol. Chem. 288:6140–53
    [Google Scholar]
43. 43.

    Demura K, Kusakizako T, Shihoya W, Hiraizumi M, Nomura K et al. 2020. Cryo-EM structures of calcium homeostasis modulator channels in diverse oligomeric assemblies. Sci. Adv. 6:eaba8105
    [Google Scholar]
44. 44.

    Taruno A. 2018. ATP release channels. Int. J. Mol. Sci. 19:808
    [Google Scholar]
45. 45.

    Romanov RA, Lasher RS, High B, Savidge LE, Lawson A et al. 2018. Chemical synapses without synaptic vesicles: purinergic neurotransmission through a CALHM1 channel-mitochondrial signaling complex. Sci. Signal. 11:eaao1815
    [Google Scholar]
46. 46.

    Kashio M, Wei-Qi G, Ohsaki Y, Kido MA, Taruno A. 2019. CALHM1/CALHM3 channel is intrinsically sorted to the basolateral membrane of epithelial cells including taste cells. Sci. Rep. 9:2681
    [Google Scholar]
47. 47.

    Schiffman SS, McElroy AE, Erickson RP. 1980. The range of taste quality of sodium salts. Physiol. Behav. 24:217–24
    [Google Scholar]
48. 48.

    Ye Q, Heck GL, DeSimone JA. 1991. The anion paradox in sodium taste reception: resolution by voltage-clamp studies. Science 254:724–26
    [Google Scholar]
49. 49.

    Roebber JK, Roper SD, Chaudhari N. 2019. The role of the anion in salt (NaCl) detection by mouse taste buds. J. Neurosci. 39:6224–32
    [Google Scholar]
50. 50.

    Lewandowski BC, Sukumaran SK, Margolskee RF, Bachmanov AA. 2016. Amiloride-insensitive salt taste is mediated by two populations of type III taste cells with distinct transduction mechanisms. J. Neurosci. 36:1942–53
    [Google Scholar]
51. 51.

    Rehnberg BG, MacKinnon BI, Hettinger TP, Frank ME. 1993. Anion modulation of taste responses in sodium-sensitive neurons of the hamster chorda tympani nerve. J. Gen. Physiol. 101:453–65
    [Google Scholar]
52. 52.

    Tomchik SM, Berg S, Kim JW, Chaudhari N, Roper SD. 2007. Breadth of tuning and taste coding in mammalian taste buds. J. Neurosci. 27:10840–48
    [Google Scholar]
53. 53.

    Yoshida R, Miyauchi A, Yasuo T, Jyotaki M, Murata Y et al. 2009. Discrimination of taste qualities among mouse fungiform taste bud cells. J. Physiol. 587:4425–39
    [Google Scholar]
54. 54.

    Meyerhof W, Batram C, Kuhn C, Brockhoff A, Chudoba E et al. 2010. The molecular receptive ranges of human TAS2R bitter taste receptors. Chem. Senses 35:157–70
    [Google Scholar]
55. 55.

    Baird TT Jr., Waheed A, Okuyama T, Sly WS, Fierke CA. 1997. Catalysis and inhibition of human carbonic anhydrase IV. Biochemistry 36:2669–78
    [Google Scholar]
56. 56.

    Zhu XL, Sly WS. 1990. Carbonic anhydrase IV from human lung. Purification, characterization, and comparison with membrane carbonic anhydrase from human kidney. J. Biol. Chem. 265:8795–801
    [Google Scholar]
57. 57.

    Kasahara Y, Narukawa M, Ishimaru Y, Kanda S, Umatani C et al. 2021. TMC4 is a novel chloride channel involved in high-concentration salt taste sensation. J. Physiol. Sci. 71:23
    [Google Scholar]
58. 58.

    Elliott EJ, Simon SA. 1990. The anion in salt taste: a possible role for paracellular pathways. Brain Res. 535:9–17
    [Google Scholar]
59. 59.

    Dethier VG. 1968. Chemosensory input and taste discrimination in the blowfly. Science 161:389–91
    [Google Scholar]
60. 60.

    Fujishiro N, Kijima H, Morita H. 1984. Impulse frequency and action potential amplitude in labellar chemosensory neurones of Drosophila melanogaster. J. Insect Physiol. 30:317–25
    [Google Scholar]
61. 61.

    Matthews BJ, Younger MA, Vosshall LB 2019. The ion channel ppk301 controls freshwater egg-laying in the mosquito Aedes aegypti. eLife 8:e43963
    [Google Scholar]
62. 62.

    Pontes G, Latorre-Estivalis JM, Gutierrez ML, Cano A, Beron de Astrada M et al. 2022. Molecular and functional basis of high-salt avoidance in a blood-sucking insect. iScience 25:104502
    [Google Scholar]
63. 63.

    Seada MA, Ignell R, Al Assiuty AN, Anderson P 2018. Functional characterization of the gustatory sensilla of tarsi of the female polyphagous moth Spodoptera littoralis. Front. Physiol. 9:1606
    [Google Scholar]
64. 64.

    Hiroi M, Meunier N, Marion-Poll F, Tanimura T. 2004. Two antagonistic gustatory receptor neurons responding to sweet-salty and bitter taste in Drosophila. J. Neurobiol. 61:333–42
    [Google Scholar]
65. 65.

    Jaeger AH, Stanley M, Weiss ZF, Musso PY, Chan RC et al. 2018. A complex peripheral code for salt taste in Drosophila. eLife 7:e37167Demonstrates that IR76b is required for attractive sodium taste in flies.
    [Google Scholar]
66. 66.

    Zhang YV, Ni J, Montell C 2013. The molecular basis for attractive salt-taste coding in Drosophila. Science 340:1334–38Shows that fly salt is encoded by the combinatorial activation of multiple taste neuron types.
    [Google Scholar]
67. 67.

    Stocker RF. 1994. The organization of the chemosensory system in Drosophila melanogaster: a review. Cell Tissue Res. 275:3–26
    [Google Scholar]
68. 68.

    Freeman EG, Dahanukar A. 2015. Molecular neurobiology of Drosophila taste. Curr. Opin. Neurobiol. 34:140–48
    [Google Scholar]
69. 69.

    Chen YD, Dahanukar A. 2020. Recent advances in the genetic basis of taste detection in Drosophila. Cell. Mol. Life Sci. 77:1087–101
    [Google Scholar]
70. 70.

    Hiroi M, Marion-Poll F, Tanimura T. 2002. Differentiated response to sugars among labellar chemosensilla in Drosophila. Zool. Sci. 19:1009–18
    [Google Scholar]
71. 71.

    Meunier N, Marion-Poll F, Rospars JP, Tanimura T. 2003. Peripheral coding of bitter taste in Drosophila. J. Neurobiol. 56:139–52
    [Google Scholar]
72. 72.

    Wang Z, Singhvi A, Kong P, Scott K. 2004. Taste representations in the Drosophila brain. Cell 117:981–91
    [Google Scholar]
73. 73.

    Thorne N, Chromey C, Bray S, Amrein H. 2004. Taste perception and coding in Drosophila. Curr. Biol. 14:1065–79
    [Google Scholar]
74. 74.

    Thistle R, Cameron P, Ghorayshi A, Dennison L, Scott K. 2012. Contact chemoreceptors mediate male-male repulsion and male-female attraction during Drosophila courtship. Cell 149:1140–51
    [Google Scholar]
75. 75.

    Marella S, Fischler W, Kong P, Asgarian S, Rueckert E, Scott K. 2006. Imaging taste responses in the fly brain reveals a functional map of taste category and behavior. Neuron 49:285–95
    [Google Scholar]
76. 76.

    Cameron P, Hiroi M, Ngai J, Scott K. 2010. The molecular basis for water taste in Drosophila. Nature 465:91–95
    [Google Scholar]
77. 77.

    Fujii S, Yavuz A, Slone J, Jagge C, Song X, Amrein H. 2015. Drosophila sugar receptors in sweet taste perception, olfaction, and internal nutrient sensing. Curr. Biol. 25:621–27
    [Google Scholar]
78. 78.

    Weiss LA, Dahanukar A, Kwon JY, Banerjee D, Carlson JR. 2011. The molecular and cellular basis of bitter taste in Drosophila. Neuron 69:258–72
    [Google Scholar]
79. 79.

    Chen Z, Wang Q, Wang Z 2010. The amiloride-sensitive epithelial Na⁺ channel PPK28 is essential for Drosophila gustatory water reception. J. Neurosci. 30:6247–52
    [Google Scholar]
80. 80.

    Liu L, Leonard AS, Motto DG, Feller MA, Price MP et al. 2003. Contribution of Drosophila DEG/ENaC genes to salt taste. Neuron 39:133–46
    [Google Scholar]
81. 81.

    Sánchez-Alcañiz JA, Silbering AF, Croset V, Zappia G, Sivasubramaniam AK et al. 2018. An expression atlas of variant ionotropic glutamate receptors identifies a molecular basis of carbonation sensing. Nat. Commun. 9:4252
    [Google Scholar]
82. 82.

    Knecht ZA, Silbering AF, Ni L, Klein M, Budelli G et al. 2016. Distinct combinations of variant ionotropic glutamate receptors mediate thermosensation and hygrosensation in Drosophila. eLife 5:e17879
    [Google Scholar]
83. 83.

    Benton R, Vannice KS, Gomez-Diaz C, Vosshall LB. 2009. Variant ionotropic glutamate receptors as chemosensory receptors in Drosophila. Cell 136:149–62
    [Google Scholar]
84. 84.

    Abuin L, Bargeton B, Ulbrich MH, Isacoff EY, Kellenberger S, Benton R. 2011. Functional architecture of olfactory ionotropic glutamate receptors. Neuron 69:44–60
    [Google Scholar]
85. 85.

    Abuin L, Prieto-Godino LL, Pan H, Gutierrez C, Huang L et al. 2019. In vivo assembly and trafficking of olfactory ionotropic receptors. BMC Biol. 17:34
    [Google Scholar]
86. 86.

    Dweck HKM, Talross GJS, Luo Y, Ebrahim SAM, Carlson JR. 2022. Ir56b is an atypical ionotropic receptor that underlies appetitive salt response in Drosophila. Curr. Biol. 32:1776–87.e4Discovered the requirement for IR56b in fly appetitive sodium taste.
    [Google Scholar]
87. 87.

    Brown EB, Shah KD, Palermo J, Dey M, Dahanukar A, Keene AC 2021. Ir56d-dependent fatty acid responses in Drosophila uncover taste discrimination between different classes of fatty acids. eLife 10:e67878
    [Google Scholar]
88. 88.

    Chen HL, Motevalli D, Stern U, Yang CH. 2022. A functional division of Drosophila sweet taste neurons that is value-based and task-specific. PNAS 119:e2110158119
    [Google Scholar]
89. 89.

    Lee MJ, Sung HY, Jo H, Kim HW, Choi MS et al. 2017. Ionotropic receptor 76b is required for gustatory aversion to excessive Na⁺ in Drosophila. Mol. Cells 40:787–95
    [Google Scholar]
90. 90.

    McDowell SAT, Stanley M, Gordon MD. 2022. A molecular mechanism for high salt taste in Drosophila. Curr. Biol. 32:P3070–81Demonstrates the role of IR7c in fly high salt taste.
    [Google Scholar]
91. 91.

    Lee Y, Poudel S, Kim Y, Thakur D, Montell C. 2018. Calcium taste avoidance in Drosophila. Neuron 97:67–74.e4
    [Google Scholar]
92. 92.

    Kim H, Jeong YT, Choi MS, Choi J, Moon SJ, Kwon JY. 2017. Involvement of a Gr2a-expressing Drosophila pharyngeal gustatory receptor neuron in regulation of aversion to high-salt foods. Mol. Cells 40:331–38
    [Google Scholar]
93. 93.

    Stanley M, Ghosh B, Weiss ZF, Christiaanse J, Gordon MD. 2021. Mechanisms of lactic acid gustatory attraction in Drosophila. Curr. Biol. 31:3525–37.e6
    [Google Scholar]
94. 94.

    Richter CP. 1936. Increased salt appetite in adrenalectomized rats. Am. J. Physiol. 115:155–61
    [Google Scholar]
95. 95.

    Geerling JC, Loewy AD. 2008. Central regulation of sodium appetite. Exp. Physiol. 93:177–209
    [Google Scholar]
96. 96.

    Kochli A, Tenenbaum-Rakover Y, Leshem M. 2005. Increased salt appetite in patients with congenital adrenal hyperplasia 21-hydroxylase deficiency. Am. J. Physiol. Regul. Integr. Comp. Physiol. 288:R1673–81
    [Google Scholar]
97. 97.

    Wilkins L, Richter CP. 1940. A great craving for salt by a child with cortico-adrenal insufficiency. JAMA 114:866–68
    [Google Scholar]
98. 98.

    Nachman M. 1962. Taste preferences for sodium salts by adrenalectomized rats. J. Comp. Physiol. Psychol. 55:1124–29
    [Google Scholar]
99. 99.

    Lee S, Augustine V, Zhao Y, Ebisu H, Ho B et al. 2019. Chemosensory modulation of neural circuits for sodium appetite. Nature 568:93–97
    [Google Scholar]
100. 100.

     Zimmerman CA, Leib DE, Knight ZA. 2017. Neural circuits underlying thirst and fluid homeostasis. Nat. Rev. Neurosci. 18:459–69
     [Google Scholar]
101. 101.

     Chang SE, Smedley EB, Stansfield KJ, Stott JJ, Smith KS. 2017. Optogenetic inhibition of ventral pallidum neurons impairs context-driven salt seeking. J. Neurosci. 37:5670–80
     [Google Scholar]
102. 102.

     Tandon S, Simon SA, Nicolelis MA. 2012. Appetitive changes during salt deprivation are paralleled by widespread neuronal adaptations in nucleus accumbens, lateral hypothalamus, and central amygdala. J. Neurophysiol. 108:1089–105
     [Google Scholar]
103. 103.

     Tindell AJ, Smith KS, Berridge KC, Aldridge JW. 2009. Dynamic computation of incentive salience: “wanting” what was never “liked. .” J. Neurosci. 29:12220–28
     [Google Scholar]
104. 104.

     Verharen JPH, Roelofs TJM, Menting-Henry S, Luijendijk MCM, Vanderschuren L, Adan RAH. 2019. Limbic control over the homeostatic need for sodium. Sci. Rep. 9:1050
     [Google Scholar]
105. 105.

     Vachez YM, Tooley JR, Abiraman K, Matikainen-Ankney B, Casey E et al. 2021. Ventral arkypallidal neurons inhibit accumbal firing to promote reward consumption. Nat. Neurosci. 24:379–90
     [Google Scholar]
106. 106.

     Bernstein IL, Taylor EM. 1992. Amiloride sensitivity of the chorda tympani response to sodium chloride in sodium-depleted Wistar rats. Behav. Neurosci. 106:722–25
     [Google Scholar]
107. 107.

     Contreras RJ. 1977. Changes in gustatory nerve discharges with sodium deficiency: a single unit analysis. Brain Res. 121:373–78
     [Google Scholar]
108. 108.

     Contreras RJ, Frank M. 1979. Sodium deprivation alters neural responses to gustatory stimuli. J. Gen. Physiol. 73:569–94
     [Google Scholar]
109. 109.

     Walker SJ, Corrales-Carvajal VM, Ribeiro C 2015. Postmating circuitry modulates salt taste processing to increase reproductive output in Drosophila. Curr. Biol. 25:2621–30
     [Google Scholar]
110. 110.

     Yapici N, Kim YJ, Ribeiro C, Dickson BJ. 2008. A receptor that mediates the post-mating switch in Drosophila reproductive behaviour. Nature 451:33–37
     [Google Scholar]
111. 111.

     Faas MM, Melgert BN, de Vos P. 2010. A brief review on how pregnancy and sex hormones interfere with taste and food intake. Chemosens. Percept. 3:51–56
     [Google Scholar]
112. 112.

     Denton DA, Nelson JF. 1971. The effects of pregnancy and lactation on the mineral appetites of wild rabbits [Oryctolagus Cuniculus (L.)]. Endocrinology 88:31–40
     [Google Scholar]
113. 113.

     Staszko SM, Boughter JD Jr., Fletcher ML. 2020. Taste coding strategies in insular cortex. Exp. Biol. Med. 245:448–55
     [Google Scholar]
114. 114.

     Spector AC, Travers SP. 2005. The representation of taste quality in the mammalian nervous system. Behav. Cogn. Neurosci. Rev. 4:143–91
     [Google Scholar]
115. 115.

     Zhang J, Jin H, Zhang W, Ding C, O'Keeffe S et al. 2019. Sour sensing from the tongue to the brain. Cell 179:392–402.e15
     [Google Scholar]
116. 116.

     Jin H, Fishman ZH, Ye M, Wang L, Zuker CS 2021. Top-down control of sweet and bitter taste in the mammalian brain. Cell 184:257–71.e16
     [Google Scholar]
117. 117.

     Barretto RP, Gillis-Smith S, Chandrashekar J, Yarmolinsky DA, Schnitzer MJ et al. 2015. The neural representation of taste quality at the periphery. Nature 517:373–76
     [Google Scholar]
118. 118.

     Wu A, Dvoryanchikov G, Pereira E, Chaudhari N, Roper SD. 2015. Breadth of tuning in taste afferent neurons varies with stimulus strength. Nat. Commun. 6:8171
     [Google Scholar]
119. 119.

     Tamura R, Norgren R. 1997. Repeated sodium depletion affects gustatory neural responses in the nucleus of the solitary tract of rats. Am. J. Physiol. 273:R1381–91
     [Google Scholar]
120. 120.

     Chen X, Gabitto M, Peng Y, Ryba NJ, Zuker CS. 2011. A gustotopic map of taste qualities in the mammalian brain. Science 333:1262–66
     [Google Scholar]
121. 121.

     Zotterman Y, Diamant H. 1959. Has water a specific taste?. Nature 183:191–92
     [Google Scholar]
122. 122.

     Hellekant G, Ninomiya Y. 1994. Bitter taste in single chorda tympani taste fibers from chimpanzee. Physiol. Behav. 56:1185–88
     [Google Scholar]
123. 123.

     Hellekant G, Ninomiya Y. 1991. On the taste of umami in chimpanzee. Physiol. Behav. 49:927–34
     [Google Scholar]
124. 124.

     Hellekant G, DuBois GE, Roberts TW, van der Wel H. 1988. On the gustatory effect of amiloride in the monkey (Macaca mulatto). Chem. Senses 13:89–93
     [Google Scholar]
125. 125.

     Stähler 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
     [Google Scholar]
126. 126.

     Rossier O, Cao J, Huque T, Spielman AI, Feldman RS et al. 2004. Analysis of a human fungiform papillae cDNA library and identification of taste-related genes. Chem. Senses 29:13–23
     [Google Scholar]
127. 127.

     Huque T, Cowart BJ, Dankulich-Nagrudny L, Pribitkin EA, Bayley DL et al. 2009. Sour ageusia in two individuals implicates ion channels of the ASIC and PKD families in human sour taste perception at the anterior tongue. PLOS ONE 4:e7347
     [Google Scholar]
128. 128.

     Dias AG, Rousseau D, Duizer L, Cockburn M, Chiu W et al. 2013. Genetic variation in putative salt taste receptors and salt taste perception in humans. Chem. Senses 38:137–45
     [Google Scholar]
129. 129.

     Feldman GM, Mogyorosi A, Heck GL, DeSimone JA, Santos CR et al. 2003. Salt-evoked lingual surface potential in humans. J. Neurophysiol. 90:2060–64
     [Google Scholar]
130. 130.

     Feldman GM, Heck GL, Smith NL. 2009. Human salt taste and the lingual surface potential correlate. Chem. Senses 34:373–82
     [Google Scholar]
131. 131.

     Tennissen AM, McCutcheon NB. 1996. Anterior tongue stimulation with amiloride suppresses NaCl saltiness, but not citric acid sourness in humans. Chem. Senses 21:113–20
     [Google Scholar]
132. 132.

     Tennissen AM. 1992. Amiloride reduces intensity responses of human fungiform papillae. Physiol. Behav. 51:1061–68
     [Google Scholar]
133. 133.

     Smith DV, Ossebaard CA. 1995. Amiloride suppression of the taste intensity of sodium chloride: evidence from direct magnitude scaling. Physiol. Behav. 57:773–77
     [Google Scholar]
134. 134.

     Ossebaard CA, Smith DV. 1996. Amiloride suppresses the sourness of NaCl and LiCl. Physiol. Behav. 60:1317–22
     [Google Scholar]
135. 135.

     Ossebaard CA, Smith DV. 1995. Effect of amiloride on the taste of NaCl, Na-gluconate and KCl in humans: implications for Na⁺ receptor mechanisms. Chem. Senses 20:37–46
     [Google Scholar]
136. 136.

     Ossebaard CA, Polet IA, Smith DV. 1997. Amiloride effects on taste quality: comparison of single and multiple response category procedures. Chem. Senses 22:267–75
     [Google Scholar]
137. 137.

     McCutcheon NB. 1992. Human psychophysical studies of saltiness suppression by amiloride. Physiol. Behav. 51:1069–74
     [Google Scholar]
138. 138.

     Halpern BP, Darlington RB. 1998. Effects of amiloride on gustatory quality descriptions and temporal patterns produced by NaCl. Chem. Senses 23:501–11
     [Google Scholar]
139. 139.

     Desor JA, Finn J. 1989. Effects of amiloride on salt taste in humans. Chem. Senses 14:793–803
     [Google Scholar]
140. 140.

     Waldmann R, Champigny G, Bassilana F, Voilley N, Lazdunski M. 1995. Molecular cloning and functional expression of a novel amiloride-sensitive Na⁺ channel. J. Biol. Chem. 270:27411–14
     [Google Scholar]
141. 141.

     Wichmann L, Althaus M. 2020. Evolution of epithelial sodium channels: current concepts and hypotheses. Am. J. Physiol. Regul. Integr. Comp. Physiol. 319:R387–400Shows that amiloride inhibits the sour side-taste but not the saltiness of NaCl in human psychophysical experiments.
     [Google Scholar]
142. 142.

     Giraldez T, Rojas P, Jou J, Flores C, Alvarez de la Rosa D 2012. The epithelial sodium channel δ-subunit: new notes for an old song. Am. J. Physiol. Renal Physiol. 303:F328–38
     [Google Scholar]
143. 143.

     Liman ER, Zhang YV, Montell C. 2014. Peripheral coding of taste. Neuron 81:984–1000
     [Google Scholar]
144. 144.

     Roper SD, Chaudhari N. 2017. Taste buds: cells, signals and synapses. Nat. Rev. Neurosci. 18:485–97
     [Google Scholar]
145. 145.

     Ye W, Chang RB, Bushman JD, Tu YH, Mulhall EM et al. 2016. The K⁺ channel K_IR2.1 functions in tandem with proton influx to mediate sour taste transduction. PNAS 113:E229–38
     [Google Scholar]
146. 146.

     Tu YH, Cooper AJ, Teng B, Chang RB, Artiga DJ et al. 2018. An evolutionarily conserved gene family encodes proton-selective ion channels. Science 359:1047–50
     [Google Scholar]
147. 147.

     Teng B, Wilson CE, Tu YH, Joshi NR, Kinnamon SC, Liman ER. 2019. Cellular and neural responses to sour stimuli require the proton channel Otop1. Curr. Biol. 29:3647–56.e5
     [Google Scholar]
148. 148.

     Saotome K, Teng B, Tsui CCA, Lee WH, Tu YH et al. 2019. Structures of the otopetrin proton channels Otop1 and Otop3. Nat. Struct. Mol. Biol. 26:518–25
     [Google Scholar]
149. 149.

     Chang RB, Waters H, Liman ER. 2010. A proton current drives action potentials in genetically identified sour taste cells. PNAS 107:22320–25
     [Google Scholar]
150. 150.

     Bartel DL, Sullivan SL, Lavoie EG, Sevigny J, Finger TE. 2006. Nucleoside triphosphate diphosphohydrolase-2 is the ecto-ATPase of type I cells in taste buds. J. Comp. Neurol. 497:1–12
     [Google Scholar]