Abstract
The taste sensation of salt is multifaceted: table salt (NaCl) at low concentrations is perceived as a preferable taste through the salty taste receptor, while that at higher concentrations is perceived as an aversive taste through distinct pathways. In addition, Cl− is also thought to participate in taste sensation through a currently unknown mechanism. Here we describe a Cl− -ion binding and the response of taste receptor type 1 (T1r), a receptor family composing sweet/umami receptors. The T1r2a/T1r3 heterodimer from medaka fish, an amino-acid taste receptor and the sole T1r member whose structure has been solved, exhibited a specific Cl−-binding in the vicinity of the amino-acid-binding site in the ligand-binding domain (LBD) of T1r3. Notably, the Cl−-binding site is likely conserved among T1r3 from other species, including humans. The Cl−-binding at the site is considered to organize the structures of the amino-acid binding site and heterodimer interface. Indeed, the Cl−-binding was found to induce a conformational change of T1r2a/T1r3LBD at sub-mM to low-mM concentrations in a similar manner to canonical taste substances. In order to address the physiological significance of the Cl− action on T1r, single fiber responses from mouse taste nerves connected to T1r-expressing taste cells were investigated. As a result, a Cl− application increased impulse frequencies, which were inhibited by a lingual application of a T1r-specific blocker. These results suggest that the Cl− evokes taste sensations by binding to T1r, underlying a reported “sweet” taste sensation by table salt at a low concentration.
Significance statement Salt taste sensation is essential for regulating salt intake and maintaining body fluid volume and concentration. Therefore, in concentrations close to that of body fluid, the sodium ion is perceived as an appealing taste through a specific taste transduction pathway. In this study, we found that a low concentration of chloride ion, a sodium ion counter anion in table salt, is perceived via the sweet taste transduction pathway mediated by the sweet taste receptor, one of the attractive taste qualities in animals. The chloride perception system discovered in this study could be another attractive pathway for promoting salt intake in an appropriate concentration range.