Sodium and Potassium Salt Stimulation of Taste Receptor Cells: An Allosteric Model

Stimulation of taste receptors with sodium chloride, sodium acetate, sodium propionate, and the respective potassium salts gave concentration-response profiles, measured electrophysiologically, which are remarkably consistent with a two-state allosteric mechanism. The allosteric constant or equilibrium constant for the transition between the active and inactive receptor states is low, resulting in a condition in which small differences in ion affinities for the two states are sufficient to significantly alter the equilibrium. Receptor activators, such as sodium ion, displaced the equilibrium toward the active receptor state by virtue of a higher affinity for that state, whereas receptor inhibitors, such as acetate and propionate ions, displaced the equilibrium in the opposite direction as a result of a higher affinity for the inactive state. The low allosteric constant increased about 10-fold after treatment with the protein modification reagent dimethyl(2-hydroxy-5-nitrobenzyl)sulfonium bromide, resulting in a marked reduction in the response to sodium chloride and sodium propionate without a significant change in ion affinities. In order to fully resolve the potassium response characteristics, it was necessary to consider both a potassium activation site and a potassium inhibition site. Analysis of the response from sodium chloride/potassium chloride mixtures showed that sodium ion is competitive with potassium binding at the activation site but not the inhibition site. With potassium propionate as the stimulus, the effect of both a receptor activator and a receptor inhibitor was quantitatively consistent with depression of the response below a water baseline level at low stimulus concentrations. Estimation of active and inactive state dissociation constants for each anion and cation permitted accurate prediction of the response magnitude for a range of cation ratios in sodium chloride/potassium chloride mixtures and anion ratios in sodium chloride/sodium propionate mixtures. The association of salty taste with receptor activators and bitter taste with receptor inhibitors may be relevant to the generation of these taste qualities.