Breza JM, Contreras RJ. Anion size modulates salt taste in rats. J Neurophysiol 107: 1632-1648, 2012. First published December 28, 2011 doi:10.1152/jn.00621.2011.-The purpose of this study was to investigate the influence of anion size and the contribution of the epithelial sodium channel (ENaC) and the transient receptor potential vanilloid-1 (TRPV1) channel on sodium-taste responses in rat chorda tympani (CT) neurons. We recorded multiunit responses from the severed CT nerve and single-cell responses from intact, narrowly tuned and broadly tuned, salt-sensitive neurons in the geniculate ganglion simultaneously with stimulus-evoked summated potentials to signal when the stimulus contacted the lingual epithelium. Artificial saliva served as the rinse and solvent for all stimuli (0.3 M NH 4 Cl, 0.5 M sucrose, 0.03-0.5 M NaCl, 0.01 M citric acid, 0.02 M quinine hydrochloride, 0.1 M KCl, and 0.03-0.5 M Na-gluconate). We used the pharmacological antagonist benzamil to assess NaCl responses mediated by ENaC, and SB-366791 and cetylpyridinium chloride to assess responses mediated by TRPV1. CT nerve responses were greater to NaCl than Na-gluconate at each concentration; this was attributed mostly to broadly tuned, acid-generalist neurons that responded with higher frequency and shorter latency to NaCl than Na-gluconate. In contrast, narrowly tuned NaCl-specialist neurons responded more similarly to the two salts, but with subtle differences in temporal pattern. Benzamil reduced CT nerve and single-cell responses only of narrowly tuned neurons to NaCl. Surprisingly, SB-366791 and cetylpyridinium chloride were without effect on CT nerve or single-cell NaCl responses. Collectively, our data demonstrate the critical role that apical ENaCs in fungiform papillae play in processing information about sodium by peripheral gustatory neurons; the role of TRPV1 channels is an enigma. chorda tympani; geniculate ganglion; epithelial sodium channel; transient receptor potential vanilloid-1; electrophysiology SALT-TASTE DETECTION DEPENDS upon two salt-sensing transduction pathways that involve specialized membrane channels on the surface of fungiform taste bud cells in rats. One is the well-documented epithelial sodium channel (ENaC) that is selective for the sodium cation and can be blocked pharmacologically by amiloride. The other is not well understood in the rodent taste system, but has recently been hypothesized to be a variant of the nonspecific-cation channel of the transient receptor potential (TRP) family, TRP vanilloid-1 (TRPV1t) (Lyall et al. 2004), which is broadly receptive to several cations, sodium as well as potassium, calcium, and ammonium. These two salt-sensing pathways in fungiform taste bud cells communicate with two divergent afferent neuron groups in the chorda tympani (CT) nerve. Narrowly tuned NaCl-specialist neurons respond selectively to sodium (and lithium) salts and little, if at all, to other salts or other basic taste stimuli. ENaC antagonists attenuate NaCl responses of NaCl-specialist neurons, but not...