We investigated the regulation of the benzamil (Bz)-insensitive salt taste receptor by intracellular Ca²⁺ ([Ca²⁺]_i), protein kinase C (PKC) and the Ca²⁺-dependent serine-threonine phosphatase, calcineurin (PP2B), by monitoring chorda tympani taste nerve responses to 0.1 M NaCl solutions containing Bz (5x10^-6 M) and resiniferatoxin (RTX; 0-10x10^-6 M) in Sprague-Dawley rats and in wildtype (WT) and TRPV1 knockout (KO) mice. In rats and WT mice, RTX increased both the phasic and tonic NaCl+BZ chorda tympani responses monotonically between 0.25x10^-6 M and 1x10^-6 M and inhibited the responses above 1x10^-6 M. Decreasing taste receptor cell [Ca²⁺]_i with BAPTA-AM, activation of PKC with 4-phorbol 12, 13-didecanoate (PMA) or the inhibition of PP2B by cyclosporine A or FK-506, enhanced the magnitude of the Bz-insensitive NaCl chorda tympani responses in the presence of RTX and either minimized or completely eliminated the decrease in the chorda tympani response above 1x10^-6 M RTX. In contrast, increasing taste receptor cell [Ca²⁺]_i with ionomycin, inhibited the Bz-insensitive NaCl chorda tympani responses in the presence of RTX. No effect of the above modulators was observed on the chorda tympani responses in WT mice and rats in the presence of TRPV1 blocker N-(3-methoxyphenyl)-4-chlorocinnamid (SB-366791; 1x10^-6 M) or in TRPV1 KO mice. ³²P labeling demonstrated direct phosphorylation of TRPV1 or TRPV1t in anterior lingual epithelium by PMA, cyclosporin A or FK-506. PMA also enhanced the RTX-sensitive unilateral apical Na⁺ flux in polarized fungiform taste receptor cells in vitro. We conclude that either the TRPV1 cation channel or its variant, TRPV1t is phosphorylated and dephosphorylated by PKC and PP2B, respectively, and either sensitizes or desensitizes the Bz-insensitive NaCl chorda tympani responses to RTX stimulation.