The cells and peripheral representation of sodium taste in mice

Abstract

Salt taste in mammals can trigger two divergent behavioural responses. In general, concentrated saline solutions elicit robust behavioural aversion, while low concentrations of NaCl are typically attractive, particularly after sodium depletion1-5. Notably, the attractive salt pathway is selectively responsive to sodium and inhibited by amiloride, while the aversive one functions as a non-selective detector for a wide range of salts1-3, 6-9. Since 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, 6-14. Here, we examine the basis of sodium sensing in the mammalian taste system. Previously, we showed that four of the five basic taste qualities, sweet, sour, bitter and umami are mediated by separate taste receptor cells (TRC) each tuned to a single taste modality, and wired to elicit stereotypical behavioural responses5, 15-18. We now demonstrate 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.

Deletion of the ubiquitin ligase Nedd4L in lung epithelia causes cystic fibrosis-like disease

“…Mutation of these PY motifs leads to impaired binding to Nedd4L, impaired channel ubiquitination, and endocytosis, and thus to increased cell-surface stability and function of ENaC (11,(14)(15)(16), which results in increased fluid absorption in the kidney (17). Although ENaC is expressed in both airway and alveolar type II epithelia (18,19) (much like Nedd4L, as our preliminary results suggest) and plays an important role in fluid absorption in the lung, especially at birth (20), the function of Nedd4L in that tissue is unclear and no genetic models have been described. Here we show that specific ablation of Nedd4L in lung epithelia in mice leads to the development of cystic fibrosis-like symptoms, most likely caused by increased ENaC function.…”

Genetics of Taste and Smell

“…112 Evolutionary forces may have shaped the human ability to recognize salty taste in such a way as to make it very responsive to differences in the environmental mineral and water supply or habitual diet. 113 Therefore, efforts to assess the impact of genetic variation within the salt receptor 114,115 should focus on salt perception of people with similar environmental backgrounds (e.g., early exposure, recent exposure) and be attentive to the current state of the subject (e.g., time of day, thirst).…”

“…114 The genes that code for the protein subunits for this channel would be a candidate target for genotype–phenotype studies in humans.…”

Taste perception, associated hormonal modulation, and nutrient intake

“…The cellular basis for the taste of salt in mice has been linked to epithelial sodium channels, which may be expressed on type I taste cells. [23][24][25] However, further research is needed to characterize the efficacy of this pathway in humans.…”