Complete the research for basic tastes receptors: the salt receptor, ENaC, validated by genetically engineered mice

A speculation, lasting over 25 years, finally is validated!

Well, as least in biological system, for any speculation, there is or will be a way to validate it. Not like mathematics or quantum physics, only God knows … I am joking :-p

Now, the Zuker group finally completed the search for the receptors for the basic tastes: bitter, salty, sweet, umami and sour.

Nature advance online publication 27 January 2010
doi:10.1038/nature08783;
Received 4 November 2009; Accepted 5 January 2010; Published online 27 January 2010

The cells and peripheral representation of sodium taste in mice

Jayaram Chandrashekar 1,4, Christina Kuhn 2,5, Yuki Oka 1,5,4, David A. Yarmolinsky 1,4, Edith Hummler 3, Nicholas J. P. Ryba 2 & Charles S. Zuker 1,4

1 Howard Hughes Medical Institute and Departments of Neurobiology and Neurosciences, University of California at San Diego, La Jolla, California 92093-0649, USA
2 National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA
3 Pharmacology and Toxicology Department, Faculty of Biology and Medicine, University of Lausanne, CH-1005 Lausanne, Switzerland
4 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.).
5 These authors contributed equally to this work.

Correspondence and requests for materials should be addressed to C.S.Z. (Email: cz2195@columbia.edu).

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 depletion 1, 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 salts 1, 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 system 1, 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 responses 5, 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 ENaC 19, 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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