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The cells and peripheral representation of sodium taste in mice

Nature volume 464, pages 297–301 (2010)Cite this article

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Abstract

Salt taste in mammals can trigger two divergent behavioural responses. In general, concentrated saline solutions elicit robust behavioural aversion, whereas low concentrations of NaCl are typically attractive, particularly after sodium depletion1,2,3,4,5. Notably, the attractive salt pathway is selectively responsive to sodium and inhibited by amiloride, whereas the aversive one functions as a non-selective detector for a wide range of salts1,2,3,6,7,8,9. Because amiloride is a potent inhibitor of the epithelial sodium channel (ENaC), ENaC has been proposed to function as a component of the salt-taste-receptor system1,3,6,7,8,9,10,11,12,13,14. Previously, we showed that four of the five basic taste qualities—sweet, sour, bitter and umami—are mediated by separate taste-receptor cells (TRCs) each tuned to a single taste modality, and wired to elicit stereotypical behavioural responses5,15,16,17,18. Here we show that sodium sensing is also mediated by a dedicated population of TRCs. These taste cells express the epithelial sodium channel ENaC19,20, and mediate behavioural attraction to NaCl. We genetically engineered mice lacking ENaCα in TRCs, and produced animals exhibiting a complete loss of salt attraction and sodium taste responses. Together, these studies substantiate independent cellular substrates for all five basic taste qualities, and validate the essential role of ENaC for sodium taste in mice.

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Figure 1: Two classes of TRCs mediate distinct salt taste responses.
Figure 2: ENaC is necessary for high sensitivity taste responses to sodium salts.
Figure 3: ENaC function in TRCs is required for behavioural attraction to salt.
Figure 4: ENaC defines a novel population of TRCs.

References

  1. Contreras, R. J. in Neural Mechanisms in Taste (ed. Cagan, R. H.) 119–145 (CRC, 1989)

    Google Scholar 

  2. Duncan, C. J. Salt preferences of birds and mammals. Physiol. Zool. 35, 120–132 (1962)

    Article  Google Scholar 

  3. Lindemann, B. Receptors and transduction in taste. Nature 413, 219–225 (2001)

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  5. Mueller, K. L. et al. The receptors and coding logic for bitter taste. Nature 434, 225–229 (2005)

    Article  ADS  CAS  Google Scholar 

  6. Eylam, S. & Spector, A. C. Taste discrimination between NaCl and KCl is disrupted by amiloride in inbred mice with amiloride-insensitive chorda tympani nerves. Am. J. Physiol. Regul. Integr. Comp. Physiol. 288, R1361–R1368 (2005)

    Article  CAS  Google Scholar 

  7. Halpern, B. P. Amiloride and vertebrate gustatory responses to NaCl. Neurosci. Biobehav. Rev. 23, 5–47 (1998)

    Article  CAS  Google Scholar 

  8. Heck, G. L., Mierson, S. & DeSimone, J. A. Salt taste transduction occurs through an amiloride-sensitive sodium transport pathway. Science 223, 403–405 (1984)

    Article  ADS  CAS  Google Scholar 

  9. Hettinger, T. P. & Frank, M. E. Specificity of amiloride inhibition of hamster taste responses. Brain Res. 513, 24–34 (1990)

    Article  CAS  Google Scholar 

  10. Doolin, R. E. & Gilbertson, T. A. Distribution and characterization of functional amiloride-sensitive sodium channels in rat tongue. J. Gen. Physiol. 107, 545–554 (1996)

    Article  CAS  Google Scholar 

  11. Kretz, O., Barbry, P., Bock, R. & Lindemann, B. 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 (1999)

    Article  CAS  Google Scholar 

  12. Schiffman, S. S., Lockhead, E. & Maes, F. W. Amiloride reduces the taste intensity of Na+ and Li+ salts and sweeteners. Proc. Natl Acad. Sci. USA 80, 6136–6140 (1983)

    Article  ADS  CAS  Google Scholar 

  13. Vandenbeuch, A., Clapp, T. R. & Kinnamon, S. C. Amiloride-sensitive channels in type I fungiform taste cells in mouse. BMC Neurosci. 9, 1 (2008)

    Article  Google Scholar 

  14. Yoshida, R. et al. NaCl responsive taste cells in the mouse fungiform taste buds. Neuroscience 159, 795–803 (2009)

    Article  CAS  Google Scholar 

  15. Huang, A. L. et al. The cells and logic for mammalian sour taste detection. Nature 442, 934–938 (2006)

    Article  ADS  CAS  Google Scholar 

  16. Yarmolinsky, D. A., Zuker, C. S. & Ryba, N. J. Common sense about taste: from mammals to insects. Cell 139, 234–244 (2009)

    Article  CAS  Google Scholar 

  17. Zhang, Y. et al. Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell 112, 293–301 (2003)

    Article  CAS  Google Scholar 

  18. Zhao, G. Q. et al. The receptors for mammalian sweet and umami taste. Cell 115, 255–266 (2003)

    Article  CAS  Google Scholar 

  19. Canessa, C. M. et al. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature 367, 463–467 (1994)

    Article  ADS  CAS  Google Scholar 

  20. Hummler, E. & Beermann, F. Scnn1 sodium channel gene family in genetically engineered mice. J. Am. Soc. Nephrol. 11, S129–S134 (2000)

    CAS  PubMed  Google Scholar 

  21. Strazzullo, P., D'Elia, L., Kandala, N. B. & Cappuccio, F. P. Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies. BMJ 10.1136/bmj.b4567 (2009)

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

    Article  ADS  CAS  Google Scholar 

  23. Oka, Y. et al. Odorant receptor map in the mouse olfactory bulb: in vivo sensitivity and specificity of receptor-defined glomeruli. Neuron 52, 857–869 (2006)

    Article  CAS  Google Scholar 

  24. Hummler, E., Merillat, A. M., Rubera, I., Rossier, B. C. & Beermann, F. Conditional gene targeting of the Scnn1a (αENaC) gene locus. Genesis 32, 169–172 (2002)

    Article  CAS  Google Scholar 

  25. Nelson, G. et al. An amino-acid taste receptor. Nature 416, 199–202 (2002)

    Article  ADS  CAS  Google Scholar 

  26. Dethier, V. G. The taste of salt. Am. Sci. 65, 744–751 (1977)

    ADS  CAS  PubMed  Google Scholar 

  27. Chandrashekar, J. et al. The taste of carbonation. Science 326, 443–445 (2009)

    Article  ADS  CAS  Google Scholar 

  28. Frank, M. E. Taste-responsive neurons of the glossopharyngeal nerve of the rat. J. Neurophysiol. 65, 1452–1463 (1991)

    Article  CAS  Google Scholar 

  29. Hellekant, G., Danilova, V. & Ninomiya, Y. Primate sense of taste: behavioral and single chorda tympani and glossopharyngeal nerve fiber recordings in the rhesus monkey, Macaca mulatta . J. Neurophysiol. 77, 978–993 (1997)

    Article  CAS  Google Scholar 

  30. Hellekant, G. & Ninomiya, Y. Bitter taste in single chorda tympani taste fibers from chimpanzee. Physiol. Behav. 56, 1185–1188 (1994)

    Article  CAS  Google Scholar 

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Acknowledgements

We thank W. Guo and A. Becker for generation and maintenance of mouse lines, and K. Scott and members of our laboratories for valuable comments. This research was supported in part by the intramural research program of the NIH, NIDCR (N.J.P.R.). C.S.Z. is an investigator of the Howard Hughes Medical Institute.

Author Contributions J.C. designed the study, carried out electrophysiological and expression studies, analysed data and wrote the paper; C.K. designed and carried out behavioural experiments and analysed expression in engineered and knockout mice; Y.O. designed and carried out calcium imaging experiments and analysed data; D.A.Y. carried out molecular studies and helped write the paper; E.H. provided essential reagents; N.J.P.R. and C.S.Z. designed the study, analysed data and wrote the paper.

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Author notes

  1. Jayaram Chandrashekar, Yuki Oka, David A. Yarmolinsky & Charles S. Zuker

    Present address: Present addresses: Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA (J.C.); Departments of Biochemistry and Molecular Biophysics and of Neuroscience, Howard Hughes Medical Institute, Columbia College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA (Y.O., D.A.Y., C.S.Z.).,

  2. Christina Kuhn and Yuki Oka: These authors contributed equally to this work.

Authors and Affiliations

  1. Howard Hughes Medical Institute and Departments of Neurobiology and Neurosciences, University of California at San Diego, La Jolla, California 92093-0649, USA,

    Jayaram Chandrashekar, Yuki Oka, David A. Yarmolinsky & Charles S. Zuker

  2. National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA ,

    Christina Kuhn & Nicholas J. P. Ryba

  3. Pharmacology and Toxicology Department, Faculty of Biology and Medicine, University of Lausanne, CH-1005 Lausanne, Switzerland

    Edith Hummler

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Correspondence to Charles S. Zuker.

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C.S.Z. is a scientific founder and scientific advisory board member of Senomyx.

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Chandrashekar, J., Kuhn, C., Oka, Y. et al. The cells and peripheral representation of sodium taste in mice. Nature 464, 297–301 (2010). https://doi.org/10.1038/nature08783

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