Eylam, Shachar, and Alan C. Spector. Taste discrimination between NaCl and KCl is disrupted by amiloride in inbred mice with amiloride-insensitive chorda tympani nerves. Am J Physiol Regul Integr Comp Physiol 288: R1361-R1368, 2005 doi:10.1152/ajpregu.00796.2004.-The amiloride-sensitive salt transduction pathway is thought to be critical for the discrimination between sodium and nonsodium salts in rodents. In rats, lingual application of amiloride appears to render NaCl qualitatively indistinguishable from KCl. In this study, we tested four strains of mice for salt discriminability. In one strain (C57BL/6J), chorda tympani nerve (CT) responses to NaCl are attenuated by amiloride, and in the other three strains (BALB/cByJ, 129P3/J, DBA/2J) they are not. Under water-restriction conditions, these mice (7 mice/strain) were trained in a gustometer to lick for water from one reinforcement spout in response to a five-lick presentation of NaCl and to lick from another in response to KCl [salt concentration was varied (0.1-1 M) to render intensity irrelevant]. Mice were then tested with the stimuli dissolved in amiloride hydrochloride, and the latter was used as the reinforcer as well. Each concentration of amiloride (0.1-100 M) was used on 2 separate days with control sessions interposed. Mice from all four strains were able to discriminate NaCl from KCl reliably. Amiloride impaired this discrimination in a dose-dependent fashion. Moreover, performance on NaCl trials appeared to be more affected by amiloride than that on KCl trials in all four strains. Thus, in contrast to the predictions based on CT recordings, discrimination in all four strains appeared to depend on the amiloride-sensitive transduction pathway, which, in the case of BALB/cByJ, 129P3/J, and DBA/2J (and perhaps C57BL/6 as well), may exist in taste buds innervated by nerves other than the CT. animal psychophysics; taste transduction; taste coding; C57BL/6; BALB/c; 129P3/J; DBA/2 THE TASTE OF SODIUM CHLORIDE appears to be transduced via at least two mechanisms, one which is selective for Na ϩ (and Li ϩ ) and is disrupted by the lingual application of the epithelial Na ϩ channel-blocker amiloride (e.g., Refs. 1,3,5,8,12,16,27, 39), and the other(s) which is amiloride-insensitive and cation nonselective (e.g., 12,17,20,22,30,[35][36][37]. In rats, electrophysiological recordings from the chorda tympani (CT) nerve have demonstrated that, when amiloride is applied to the lingual epithelium, the responsiveness of this nerve to sodium salts, but not to nonsodium salts, is markedly suppressed (e.g., Refs. 3,8,12,16,27,36).Evidence supporting the importance of the amiloride-sensitive mechanism to sodium-specific taste comes from behavioral studies. Amiloride appears to render NaCl qualitatively indistinguishable from KCl in a dose-dependent fashion (e.g., Ref. 18,33). This is evident both in discrimination studies, where adulteration of the taste solutions with amiloride reduces the ability of rats to discriminate NaCl from KCl salt to chance levels (21, 33), a...