A Na ⁺ -selective High-salt Taste Receptor Mediates State-Dependent Sodium Aversion

Animals balance sodium intake by seeking low concentrations to meet physiological needs while avoiding toxic excess. However, how internal state selectively regulates high-sodium aversion remains unknown. Here, we identify the first Na ⁺ -selective high-salt taste receptor and demonstrate its essential role in internal-state-dependent sodium avoidance. In Drosophila , the ionotropic receptor IR11a, together with co-receptor IR25a, functions in bitter gustatory receptor neurons (GRNs) to mediate aversion to high Na ⁺ . Loss of IR11a abolishes neuronal and behavioral responses to Na ⁺ and Li ⁺ , while sparing detection of K ⁺ , Ca ²⁺ , and bitter compounds. Heterologous expression confirms that IR11a and IR25a form a Na ⁺ -selective channel. Notably, sodium deprivation or satiety specifically modulates Na ⁺ sensitivity in IR11a ⁺ GRNs—without altering responses to K ⁺ or bitter stimuli—and this modulation requires the IR11a/IR25a complex. These findings reveal a dedicated, state-dependent Na ⁺ -sensing pathway embedded within aversive taste cells, providing a peripheral mechanism for adaptive sodium consumption based on physiological need.