The proposal deals with the mechanism of transduction in mammalian taste reception. A new method for detecting the effects of tastants at the single cell level is introduced. The method permits tastants to be applied to the normal taste-sensitive regions of the taste-bud while at the same time recording the cell electrical response. Recordings are made using patch-clamp technology. With these methods the characteristics of the cells in the anterior part of the rat tongue will be examined. Single fiber analysis of the rat chorda tympani suggests the existence of cells that will have a highly selective sodium ion conductance in the cell apical membrane. There should also be less selective cells reactive to various salts and acids. A catalog of cell types will be made to test this hypothesis. The kinetics of the changing intracellular potential will be studied under conditions of normal chemical stimulation. The possible presence of action potentials will be noted and the kinetics of cellular adaptation will be studied. Preliminary data show that the apical membranes of some taste cells have amiloride-blockade conductances. The ion specificity of these amiloride-sensitive apical membrane conductances will be examined. The possible involvement of cAMP in the sweet taste transduction will be explored. This will be done on the single cell level, and also using a live-rat model in which the chorda tympani response to sucrose will be measured with changes in the transepithelial potential or current under voltage clamp. Preliminary data indicate that a basolateral membrane conductance is blocked during stimulation by sucrose. The question of the regulation of the expression of amiloride-blockade sodium conductances will be addresses. Among sodium-deprived rats there is evidence that regulation may be effected through sodium-regulating hormones. We shall explore this possibility electrophysiologically at the cellular level and with a live-rat model. Atrial natriuretic factor, acting via cGMP, is one of the possible regulatory substances. Taste is a major factor in determining food intake. The conditions and substances that modulate its expression will have a strong impact in the areas of sodium-sensitive hypertension and feeding disorders such as obesity.
