The sense of smell plays 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 our chemosensory competence. Receptor neurons in the nose serve the critical function of detecting and transducing odorants. Disruption of any of the intracellular events leading to receptor cell activation can result in olfactory dysfunction. Emerging evidence implicates phosphoinositide signaling and the transient receptor potential (TRP) ion channels commonly targeted by this signaling pathway in chemosensory transduction in taste receptor cells, vomeronasal receptor neurons, invertebrate olfactory receptor neurons, and possibly in vertebrate olfactory receptor neurons, where recent evidence suggests it can modulate the well established cyclic nucleotide signaling pathway. Phosphoinositide signaling is inherently complex, and this complexity has impeded a clear understanding of its role in many cellular systems. In this continuing project, we use an integrated, molecular, biochemical, and electrophysiologicalapproach to further define the cellular mechanisms of phosphoinositide signaling in an olfactory system. We use an animal model in which the functional role of phosphoinositide signaling in olfactory transduction is particularly well established, and has led to the evidence suggesting a potential role for phosphoinositide signaling in vertebrate olfaction. This project has the potential to identify new cellular and molecular events potentially involved in olfactory receptor cell activation, as well as contribute to a more general understanding of phospholipid signaling and TRP channel function in chemical sensing.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC001655-17
Application #
7727375
Study Section
Special Emphasis Panel (ZRG1-IFCN-F (03))
Program Officer
Davis, Barry
Project Start
1992-08-01
Project End
2011-11-30
Budget Start
2009-12-01
Budget End
2011-11-30
Support Year
17
Fiscal Year
2010
Total Cost
$293,356
Indirect Cost
Name
University of Florida
Department
Type
Organized Research Units
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
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
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
Ukhanov, K; Bobkov, Y; Ache, B W (2011) Imaging ensemble activity in arthropod olfactory receptor neurons in situ. Cell Calcium 49:100-7
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

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