Our long range goal is to elucidate Ion mechanisms of primary events in olfaction culminated in excitation or inhibition of olfactory receptor neurons (ORN) in normal functions of the olfactory system and its disorders. Although role of ciliary ion channels in the primary excitatory reactions is known, the participation of these channels in the termination of the odor-evoked responses are not very well understood. The objective of this application is to define and characterize the ion channel events associated with termination of odorant responses of ORN by studying native rat ORN and olfactory odorant receptors reconstituted in bilayers. The central hypothesis ' to be tested is that ciliary ion channels and their modulation are critical for down-regulation of ORN activity evoked by odorants. The rationale behind the research is that ciliary ion channels directly express the level of neuronal state by values of ion currents and the modulation of these channels is known to effect the te rmination of the odor-evoked currents. Therefore the down-regulation of ion channels is expected to be as important as the control of any step in the olfactory signal transduction cascade. Specifically we propose to: i) determine the role of cyclic nucleotide-gated (CNG) channels in suppression of odorant responses by odorants in ORN; ii) determine kinetics of CNG channels accounted for Ca2+adaptation of ORN; and iii) characterize ion currents, controlled ' by second messengers and Ca2+, causing the hyperpolarization and inhibition of ORN. These results will -provide a better understanding of the role of ciliary ion channels in molecular mechanisms of olfactory reception and transduction.
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