Skip to main content

Advertisement

SpringerLink
Log in

A Role of the Epithelial Sodium Channel in Human Salt Taste Transduction?

  • Published:
Chemosensory Perception

Abstract

Mammals perceive the five different taste qualities: bitter, sweet, umami, sour, and salty. At least two different mechanisms contribute to salt taste in rodents. One is elicited by various cations and sensitive to cetylpyridinium chloride, whereas another is selectively stimulated by Na+ and inhibited by amiloride. The latter pathway has been suggested to involve the epithelial sodium channel, ENaC. In humans, the presence of amiloride-sensitive salt taste transduction is being disputed. In this paper, we addressed the question whether ENaC may have a role in human salt taste perception. Immunohistochemistry revealed that β-, γ-, and δ-ENaC subunits are present in subsets of circumvallate and fungiform taste bud cells, whereas α-ENaC was confined to cells of circumvallate taste buds. Alpha-, β-, and γ-subunits were observed in basolateral intracellular compartments, while δ-ENaC was exclusively found in all taste pores of both types of papillae consistent with a function in taste transduction. To further assess the involvement of ENaC in salt taste transduction, we combined sensory studies and functional expression of ENaC in oocytes. With the exception of l-homoarginine, choline chloride, l-arginine, l-lysine, and l-argininyl-l-arginine enhanced both salt taste perception in subjects and sodium currents recorded in αβγ- or δβγ-ENaC expressing oocytes, whereas l-glutamine did neither show salt-taste-enhancing activity nor did it influence the sodium currents in the oocyte assay. Taken together, our data make ENaC an interesting molecule possibly involved in salty taste transduction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS (2000) A novel family of mammalian taste receptors. Cell 100:693–702

    Article  CAS  Google Scholar 

  • Anand KK, Zuniga JR (1997) Effect of amiloride on suprathreshold NaCl, LiCl, and KCl salt taste in humans. Physiol Behav 62:925–929

    Article  CAS  Google Scholar 

  • Avenet P, Lindemann B (1988) Amiloride-blockable sodium currents in isolated taste receptor cells. J Membr Biol 105:245–255

    Article  CAS  Google Scholar 

  • Beauchamp GK, Bertino M, Burke D, Engelman K (1990) Experimental sodium depletion and salt taste in normal human volunteers. Am J Clin Nutr 51:881–889

    CAS  Google Scholar 

  • Behrens M, Stähler F, Shi P, Bufe B, Meyerhof W (2007) Taste: topics in chemical biology. Wiley Encyclopedia of Chemical Biology

  • Boughter JD Jr., Gilbertson TA (1999) From channels to behavior: an integrative model of NaCl taste. Neuron 22:213–215

    Article  CAS  Google Scholar 

  • Brand JG, Teeter JH, Silver WL (1985) Inhibition by amiloride of chorda tympani responses evoked by monovalent salts. Brain Res 334:207–214

    Article  CAS  Google Scholar 

  • Brouard M, Casado M, Djelidi S, Barrandon Y, Farman N (1999) Epithelial sodium channel in human epidermal keratinocytes: expression of its subunits and relation to sodium transport and differentiation. J Cell Sci 112(Pt 19):3343–3352

    CAS  Google Scholar 

  • Bufe B, Hofmann T, Krautwurst D, Raguse JD, Meyerhof W (2002) The human TAS2R16 receptor mediates bitter taste in response to beta-glucopyranosides. Nat Genet 32:397–401

    Article  CAS  Google Scholar 

  • Contreras RJ, Catalanotto FA (1980) Sodium deprivation in rats: salt thresholds are related to salivary sodium concentrations. Behav Neural Biol 29:303–314

    Article  CAS  Google Scholar 

  • Denton D (1982) The hunger for salt. An anthropological, physiological and medical analysis. Springer, Berlin

    Google Scholar 

  • 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 83:633–656

    Article  CAS  Google Scholar 

  • DeSimone JA, Lyall V, Heck GL, Phan TH, Alam RI, Feldman GM, Buch RM (2001) A novel pharmacological probe links the amiloride-insensitive NaCl, KCl, and NH(4)Cl chorda tympani taste responses. J Neurophysiol 86:2638–2641

    CAS  Google Scholar 

  • Doolin RE, Gilbertson TA (1996) Distribution and characterization of functional amiloride-sensitive sodium channels in rat tongue. J Gen Physiol 107:545–554

    Article  CAS  Google Scholar 

  • Feldman GM, Mogyorosi A, Heck GL, DeSimone JA, Santos CR, Clary RA, Lyall V (2003) Salt-evoked lingual surface potential in humans. J Neurophysiol 90:2060–2064

    Article  Google Scholar 

  • Formaker BK, Hill DL (1991) Lack of amiloride sensitivity in SHR and WKY glossopharyngeal taste responses to NaCl. Physiol Behav 50:765–769

    Article  CAS  Google Scholar 

  • Gilbertson TA, Fontenot DT (1998) Distribution of amiloride-sensitive sodium channels in the oral cavity of the hamster. Chem Senses 23:495–499

    Article  CAS  Google Scholar 

  • Gilbertson TA, Kinnamon SC (1996) Making sense of chemicals. Chem Biol 3:233–237

    Article  CAS  Google Scholar 

  • Guitard M, Leyvraz C, Hummler E (2004) A nonconventional look at ionic fluxes in the skin: lessons from genetically modified mice. News Physiol Sci 19:75–79

    CAS  Google Scholar 

  • Hager H, Kwon TH, Vinnikova AK, Masilamani S, Brooks HL, Frokiaer J, Knepper MA, Nielsen S (2001) Immunocytochemical and immunoelectron microscopic localization of alpha-, beta-, and gamma-ENaC in rat kidney. Am J Physiol Renal Physiol 280:F1093–F1106

    CAS  Google Scholar 

  • Halpern BP (1998) Amiloride and vertebrate gustatory responses to NaCl. Neurosci Biobehav Rev 23:5–47

    Article  CAS  Google Scholar 

  • Halpern BP, Darlington RB (1998) Effects of amiloride on gustatory quality descriptions and temporal patterns produced by NaCl. Chem Senses 23:501–511

    Article  CAS  Google Scholar 

  • Heck GL, Mierson S, DeSimone JA (1984) Salt taste transduction occurs through an amiloride-sensitive sodium transport pathway. Science 223:403–405

    Article  CAS  Google Scholar 

  • Hubbard TJ, Aken BL, Beal K, Ballester B, Caccamo M, Chen Y, Clarke L, Coates G, Cunningham F, Cutts T, Down T, Dyer SC, Fitzgerald S, Fernandez-Banet J, Graf S, Haider S, Hammond M, Herrero J, Holland R, Howe K, Johnson N, Kahari A, Keefe D, Kokocinski F, Kulesha E, Lawson D, Longden I, Melsopp C, Megy K, Meidl P, Ouverdin B, Parker A, Prlic A, Rice S, Rios D, Schuster M, Sealy I, Severin J, Slater G, Smedley D, Spudich G, Trevanion S, Vilella A, Vogel J, White S, Wood M, Cox T, Curwen V, Durbin R, Fernandez-Suarez XM, Flicek P, Kasprzyk A, Proctor G, Searle S, Smith J, Ureta-Vidal A, Birney E (2007) Ensembl 2007. Nucleic Acids Res 35:D610–D617

    Article  CAS  Google Scholar 

  • Ji HL, Bishop LR, Anderson SJ, Fuller CM, Benos DJ (2004) The role of Pre-H2 domains of alpha- and delta-epithelial Na+ channels in ion permeation, conductance, and amiloride sensitivity. J Biol Chem 279:8428–8440

    Article  CAS  Google Scholar 

  • Ji HL, Su XF, Kedar S, Li J, Barbry P, Smith PR, Matalon S, Benos DJ (2006) Delta-subunit confers novel biophysical features to alpha beta gamma-human ENaC via a physical interaction. J Biol Chem 281:8233–8241

    Article  CAS  Google Scholar 

  • Kitada Y, Mitoh Y, Hill DL (1998) Salt taste responses of the IXth nerve in Sprague–Dawley rats: lack of sensitivity to amiloride. Physiol Behav 63:945–949

    Article  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • Kuhn C, Bufe B, Winnig M, Hofmann T, Frank O, Behrens M, Lewtschenko T, Slack JP, Ward CD, Meyerhof W (2004) Bitter taste receptors for saccharin and acesulfame K. J Neurosci 24:10260–10265

    Article  CAS  Google Scholar 

  • Li WY, Huey CL, Yu AS (2004) Expression of claudin-7 and -8 along the mouse nephron. Am J Physiol Renal Physiol 286:F1063–F1071

    Article  CAS  Google Scholar 

  • Liman ER, Tytgat J, Hess P (1992) Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs. Neuron 9:861–871

    Article  CAS  Google Scholar 

  • Lin W, Finger TE, Rossier BC, Kinnamon SC (1999) Epithelial Na+ channel subunits in rat taste cells: localization and regulation by aldosterone. J Comp Neurol 405:406–420

    Article  CAS  Google Scholar 

  • Lindemann B (1996) Taste reception. Physiol Rev 76:718–766

    CAS  Google Scholar 

  • Locke KW, Fielding S (1994) Enhancement of salt intake by choline chloride. Physiol Behav 55:1039–1046

    Article  CAS  Google Scholar 

  • McCaughey SA, Scott TR (1998) The taste of sodium. Neurosci Biobehav Rev 22:663–676

    Article  CAS  Google Scholar 

  • McDonald FJ, Snyder PM, McCray PB, Jr., Welsh MJ (1994) Cloning, expression, and tissue distribution of a human amiloride-sensitive Na+ channel. Am J Physiol 266:L728–L734

    CAS  Google Scholar 

  • McDonald FJ, Price MP, Snyder PM, Welsh MJ (1995) Cloning and expression of the beta- and gamma-subunits of the human epithelial sodium channel. Am J Physiol 268:C1157–C1163

    CAS  Google Scholar 

  • Michlig S, Damak S, Le Coutre J (2007) Claudin-based permeability barriers in taste buds. J Comp Neurol 502:1003–1011

    Article  CAS  Google Scholar 

  • Miyamoto T, Miyazaki T, Fujiyama R, Okada Y, Sato T (2001) Differential transduction mechanisms underlying NaCl- and KCl-induced responses in mouse taste cells. Chem Senses 26:67–77

    Article  CAS  Google Scholar 

  • Ninomiya Y (1998) Reinnervation of cross-regenerated gustatory nerve fibers into amiloride-sensitive and amiloride-insensitive taste receptor cells. Proc Natl Acad Sci USA 95:5347–5350

    Article  CAS  Google Scholar 

  • Ogawa T, Nakamura T, Tsuji E, Miyanaga Y, Nakagawa H, Hirabayashi H, Uchida T (2004) The combination effect of L-arginine and NaCl on bitterness suppression of amino acid solutions. Chem Pharm Bull (Tokyo) 52:172–177

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Rossier O, Cao J, Huque T, Spielman AI, Feldman RS, Medrano JF, Brand JG, le Coutre J (2004) Analysis of a human fungiform papillae cDNA library and identification of taste-related genes. Chem Senses 29:13–23

    Article  CAS  Google Scholar 

  • Rotzoll N, Dunkel A, Hofmann T (2006) Quantitative studies, taste reconstitution, and omission experiments on the key taste compounds in morel mushrooms (Morchella deliciosa Fr.). J Agric Food Chem 54:2705–2711

    Article  CAS  Google Scholar 

  • Schiffman SS, Lockhead E, Maes FW (1983) Amiloride reduces the taste intensity of Na+ and Li+ salts and sweeteners. Proc Natl Acad Sci USA 80:6136–6140

    Article  CAS  Google Scholar 

  • Shigemura N, Islam AA, Sadamitsu C, Yoshida R, Yasumatsu K, Ninomiya Y (2005) Expression of amiloride-sensitive epithelial sodium channels in mouse taste cells after chorda tympani nerve crush. Chem Senses 30:531–538

    Article  CAS  Google Scholar 

  • Smith DV, Ossebaard CA (1995) Amiloride suppression of the taste intensity of sodium chloride: evidence from direct magnitude scaling. Physiol Behav 57:773–777

    Article  CAS  Google Scholar 

  • Smith DV, van der Klaauw NJ (1995) The perception of saltiness is eliminated by NaCl adaptation: implications for gustatory transduction and coding. Chem Senses 20:545–557

    Article  CAS  Google Scholar 

  • Sollars SI, Bernstein IL (1994) Amiloride sensitivity in the neonatal rat. Behav Neurosci 108:981–987

    Article  CAS  Google Scholar 

  • Tennissen AM (1992) Amiloride reduces intensity responses of human fungiform papillae. Physiol Behav 51:1061–1068

    Article  CAS  Google Scholar 

  • Tennissen AM, McCutcheon NB (1996) Anterior tongue stimulation with amiloride suppresses NaCl saltiness, but not citric acid sourness in humans. Chem Senses 21:113–120

    Article  CAS  Google Scholar 

  • Van Itallie C, Rahner C, Anderson JM (2001) Regulated expression of claudin-4 decreases paracellular conductance through a selective decrease in sodium permeability. J Clin Invest 107:1319–1327

    Article  Google Scholar 

  • 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 270:27411–27414

    Article  CAS  Google Scholar 

  • Yu AS, Enck AH, Lencer WI, Schneeberger EE (2003) Claudin-8 expression in Madin–Darby canine kidney cells augments the paracellular barrier to cation permeation. J Biol Chem 278:17350–17359

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank Ms. Elisabeth Meyer for expert technical assistance and Dr. Erwin Tareilus for the supply of cDNAs encoding α-, β- and γ-ENaC. This work was supported by grants from the Federal Ministry of Education and Research (BMBF) to W.M. (0313819A) and T.H. (0313819B).

Author information

Authors and Affiliations

  1. Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany

    Frauke Stähler, Katja Riedel, Stefanie Demgensky, Katrin Neumann, Barbara Raab, Maik Behrens & Wolfgang Meyerhof

  2. Chair of Food Chemistry und Molecular Sensory Science, Technical University of Munich, Lise-Meitner-Str. 34, 85354, Freising, Germany

    Andreas Dunkel, Alexander Täubert & Thomas Hofmann

  3. Clinic and Polyclinic for Oral and Maxillofacial Surgery and Plastic Surgery, Charité University for Medical Science of Berlin, Campus Virchow Hospital, Augustenburger Platz 1, 13353, Berlin, Germany

    Jan-Dirk Raguse

Authors
  1. Frauke Stähler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katja Riedel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefanie Demgensky
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Katrin Neumann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andreas Dunkel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alexander Täubert
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Barbara Raab
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Maik Behrens
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jan-Dirk Raguse
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Thomas Hofmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Wolfgang Meyerhof
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wolfgang Meyerhof.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Fig. S1

Immunohistochemistry omitting primary antibodies in circumvallate and fungiform papillae. Indirect immunohistochemistry was performed without primary antibodies using 2-μm sections of paraffin-embedded human circumvallate and fungiform papillae. Detection with peroxidase-conjugated secondary antibody resulted in no labeling at all. Dotted lines mark taste buds within taste papillae (GIF 103 KB).

Fig. S1 High-resolution image (TIF 2.31 MB).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stähler, F., Riedel, K., Demgensky, S. et al. A Role of the Epithelial Sodium Channel in Human Salt Taste Transduction?. Chem. Percept. 1, 78–90 (2008). https://doi.org/10.1007/s12078-008-9006-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12078-008-9006-4

Keywords

Search

Navigation