Data now clearly establish that odors activate at least two second messenger-mediated transduction pathways in olfactory receptor cells, and that they do so in phylogenetically diverse animals. As yet, the functional basis for having more than one way to activate olfactory receptor cells is unknown, even though this knowledge is fundamental to understanding the sense of smell. For example, having multiple transduction pathways co-expressed in the same cells would provide direct evidence that olfactory integration begins at the level of receptor cell, while having them expressed in different cells would indicate functional subclasses of olfactory receptor cells. Either of these heretofore unknown elements of peripheral olfactory organization have direct implications as to how odors are coded. It is proposed to combine whole cell and single channel electrophysiological recording and biochemical analyses of second messenger production to characterize cAMP and IP3-regulated olfactory transduction. The study uses an animal model for which preliminary data establish that the two transduction pathways co-exist in the same receptor cells and regulate distinct, opposing conductances that act in concert to determine the electrophysiological response of the receptor cell to complex odors. The study provides the first opportunity to investigate these two transduction pathways in a functionally defined context. Understanding olfactory transduction is fundamental to understanding the role of the receptor cell in the sense of smell and, in turn, olfactory dysfunctions caused by environmental and pathogenic insult to the receptor organ.
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