The cells and peripheral representation of sodium taste in mice

Abstract

Mammals are repelled by large concentrations of salts but attracted to low concentrations of sodium. In mice, the latter behaviour can be blocked by the ion-channel inhibitor amiloride. Now mice genetically engineered to lack the drug's target sodium channel, ENaC, in taste receptor neurons have been found to lack both salt sensing and sodium taste responses. Thus sodium sensing, like the four other taste modalities (sweet, sour, bitter and umami), is mediated by dedicated taste-receptor cells. Though because sodium sensing is amiloride-insensitive in primates, how this relates to our ability to taste salt remains unclear. Mammals are repelled by large concentrations of salts but attracted to low concentrations of sodium. In mice, the latter behaviour can be blocked by the ion channel inhibitor amiloride. Here, mice have been produced lacking the drug's target sodium channel, ENaC, specifically in taste receptor neurons. It is confirmed that sodium sensing, like the four other taste modalities (sweet, sour, bitter and umami), is mediated by a dedicated 'labelled line'. 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.