Odors play an increasingly appreciated role in our general quality of life and well being, a role that is compromised by the effect of disease, drugs, aging and environmental onslaught on olfactory competence. Primary olfactory receptor neurons serve the critical function of detecting and transducing odor stimuli. Disruption of any of the cellular processes leading to receptor cell activation would impair olfactory function. Particularly important targets would be gain-setting processes that are known to be critical control points in biological systems. Olfactory transduction is a two-stage process in which odors activate a primary second messenger cascade that secondarily triggers the main excitatory current for the cell. This strategy for achieving high-gain, low-noise amplification appears to be a fundamental organizational principle that has been conserved or converged upon in evolution. This continuing project combines electrophysiological and molecular approaches to (l) identify the factors that regulate the mail output channel and (2) further define the steps that lead to activation of this channel. The project uses an invertebrate animal model in which both phosphatidylinositol and cyclic nucleotide signaling lead to activation of the output channel. It builds on interesting preliminary evidence that what were considered to be inactive products of phosphatidylinositol metabolism, an intracellular signaling system that has been implicated in olfactory transduction in a conflicting and even controversial way, can regulate the output channel.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-4 (01))
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Davis, Barry
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University of Florida
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United States
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Bobkov, Y; Corey, E; Ache, B (2014) An inhibitor of Na(+)/Ca(2+) exchange blocks activation of insect olfactory receptors. Biochem Biophys Res Commun 450:1104-9
Ukhanov, K; Bobkov, Y; Corey, E A et al. (2014) Ligand-selective activation of heterologously-expressed mammalian olfactory receptor. Cell Calcium 56:245-56
Park, Il Memming; Bobkov, Yuriy V; Ache, Barry W et al. (2014) Intermittency coding in the primary olfactory system: a neural substrate for olfactory scene analysis. J Neurosci 34:941-52
Corey, Elizabeth A; Bobkov, Yuriy; Ukhanov, Kirill et al. (2013) Ionotropic crustacean olfactory receptors. PLoS One 8:e60551
Pask, Gregory M; Bobkov, Yuriy V; Corey, Elizabeth A et al. (2013) Blockade of insect odorant receptor currents by amiloride derivatives. Chem Senses 38:221-9
Ukhanov, Kirill; Corey, Elizabeth A; Ache, Barry W (2013) Phosphoinositide 3-kinase dependent inhibition as a broad basis for opponent coding in Mammalian olfactory receptor neurons. PLoS One 8:e61553
Bobkov, Yuriy; Park, Il; Park, Ill et al. (2012) Cellular basis for response diversity in the olfactory periphery. PLoS One 7:e34843
Bobkov, Y V; Corey, E A; Ache, B W (2011) The pore properties of human nociceptor channel TRPA1 evaluated in single channel recordings. Biochim Biophys Acta 1808:1120-8
Ukhanov, K; Bobkov, Y; Ache, B W (2011) Imaging ensemble activity in arthropod olfactory receptor neurons in situ. Cell Calcium 49:100-7
Ukhanov, Kirill; Brunert, Daniela; Corey, Elizabeth A et al. (2011) Phosphoinositide 3-kinase-dependent antagonism in mammalian olfactory receptor neurons. J Neurosci 31:273-80

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