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+, Ca2+, 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.