Date of Award:

5-2009

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Biology

Advisor/Chair:

Timothy A Gilbertson

Abstract

Nutrient recognition is one of the main physiological roles of the gustatory system. In mammals, it is well established that the taste of sodium salts is primarily mediated by sodium influx through the epithelial sodium channel. The epithelial sodium channel is a sodium-specific ion channel that is expressed across a wide range of transporting epithelia such as colon, kidney, and taste. In addition to its role as a salt taste receptor, sodium influx through the epithelial sodium channel is important systemically for maintaining sodium balance and blood pressure. Following our earlier work on the endocrine regulation of salt taste at the level of the epithelial sodium channel, we hypothesize that the epithelial sodium channel expressed in mouse taste receptor cells plays a central role in the restoration of salt and water balance. Using a multidisciplinary approach that includes patch clamp recording, functional sodium imaging, molecular biology, Western blotting, and behavioral assays, we have begun to investigate different mechanisms of the epithelial sodium channel regulation in the taste system. In the present study, we have demonstrated a number of mechanisms that regulate the epithelial sodium channel by both ions and/or hormones in mouse taste cells. In general, three new mechanisms of the epithelial sodium channel regulation were identified: (1) regulation of the epithelial sodium channel by chloride ions, (2) regulation of the epithelial sodium channel by insulin, and (3) alterations of the epithelial sodium channel function in diabetic taste cells. To test the relevance of one or more of these regulatory mechanisms in the animals' behavior, we used a variety of short-term behavioral assays. Interestingly, the results suggested that insulin regulates salt intake in rodents, which dovetails nicely with our functional and molecular findings. Consistent with insulin's physiological role in salt taste transduction, we investigated the modification of the epithelial sodium channel function during the onset of diabetes. Diabetic rodents displayed alterations in salt taste transduction via epithelial sodium channel from the gene level to the animals' behavior. These results are an example of how regulatory cues, like hormones, act on specific transduction elements to modulate the peripheral gustatory system.

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