The present proposal is part of an overall effort to understand basic and clinically relevant aspects of olfaction, in particular mechanisms of olfactory transduction in the rat. A multidisciplinary approach is proposed involving electrophysiological, biophysical, and molecular biological techniques. Experiments are proposed to understand how olfactory receptors stimulate the formation of two known olfactory second messengers, cAMP and InsP3, and how these intracellular signals regulate the membrane conductance of olfactory receptor neurons. Specifically, experiments are proposed to: (1) characterize the currents elicited by cAMP and Ins3-generating odors, (2) characterize the currents elicited by both these second messengers, (3) study the potential interaction among olfactory receptor neurons in situ in epithelial slices, (4) characterize olfactory receptor gene expression in single olfactory receptor neurons, and (5) analyze the odor specificity and sensitivity of any cloned olfactory receptor gene products in heterologous expression systems.
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