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.

Theoretical modeling of ionic distribution and transport in a nanochannel containing a surface charge on its wall, 30 nm high and 5 microm long, suggests that ionic current can be controlled by locally modifying the surface charge density through a gate electrode, even if the electrical double layers are not overlapped. When the surface charge densities at the right and left halves of a channel are the same absolute value but of different signs, this could form the basis of a nanofluidic diode. When the surface charge density at the middle part of a channel is modified, this could form the basis of a nanofluidic bipolar transistor.

In the tongue, distinct classes of taste receptor cells detect the five basic tastes, sweet, sour, bitter, sodium salt, and umami1,2. Among these qualities, bitter and sour stimuli are innately aversive, whereas sweet and umami are appetitive, and generally attractive to animals. In contrast, salty taste is unique in that increasing salt concentration fundamentally transforms an innately appetitive stimulus into a powerfully aversive one3–7. This appetitive-aversive balance helps maintain appropriate salt consumption3,4,6,8, and represents an important part of fluid and electrolyte homeostasis. We have previously shown that the appetitive responses to NaCl are mediated by taste receptor cells expressing the epithelial sodium channel, ENaC8, while the cellular substrate for salt aversion was unknown. Here we explore the cellular and molecular basis for the rejection of high concentrations of salts (>300 mM NaCl or KCl). We now show that high-salt recruits the two primary aversive taste pathways by activating the sour and bitter taste-sensing cells. We also demonstrate that genetic silencing of these pathways abolishes behavioral aversion to concentrated salt, without impairing salt attraction. Notably, mice devoid of salt-aversion pathways now exhibit unimpeded, continuous attraction even to exceedingly high concentrations of NaCl. We propose that the “co-opting” of sour and bitter neural pathways evolved as a means to ensure that high levels of salt reliably trigger robust behavioral rejection, thus preventing its potentially detrimental effects in health and well-being.