A Na+-selective receptor enables state-dependent plasticity in high-salt taste

Sodium is an essential ion, but harmful in excess. Animals must suppress sodium aversion during deficiency, yet a cation-nonselective override would expose them to other harmful salts. Whether and how the sensory periphery regulates high-salt taste to achieve Na+-specific tuning remains unknown. Here we identify a Na+-selective, state-tunable high-salt detection mechanism in Drosophila. IR11a and IR25a function in bitter gustatory receptor neurons (GRNs) and are required for aversion specifically to high Na+. Loss of IR11a abolishes responses to Na+ and Li+ while sparing detection of K+, Ca2+, and bitter compounds. Heterologous expression confirms that IR11a and IR25a together confer Na+ responsiveness. During sodium deprivation, Na+ sensitivity in IR11a-expressing neurons is decreased and restored upon satiety, allowing flies to attenuate Na+ aversion specifically. The IR7c-dependent nonselective mechanism remains insensitive to sodium deprivation, thereby preserving aversion to other noxious cations even during sodium deficiency. The IR11a-mediated response is amiloride-sensitive, a functional signature reminiscent of mammalian ENaC despite the absence of sequence homology. This work reveals that peripheral high-salt taste combines a fixed, cation-nonselective defense with a sodium-selective, physiologically tunable mechanisms, offering a candidate logic for aversive high-salt taste in vertebrates, where the molecular basis remains poorly defined.