title: Olfactory marker protein modulates the cAMP kinetics of the odour-induced response in cilia of mouse olfactory receptor neurons.
abstract: Olfactory marker protein (OMP), a phylogenetically conserved protein, is highly, and almost exclusively, expressed in vertebrate olfactory receptor neurons (ORNs). Although OMP is widely used as a marker for ORNs, its function has remained largely elusive. Here we used suction-pipette recordings from isolated ORNs of OMP(-/-) mice to investigate its role in olfactory transduction. Vertebrate olfactory transduction is initiated when odourants bind to receptor proteins to activate an adenylyl cyclase via a G protein-coupled signalling pathway. This leads to an increase in cAMP and the opening of a cyclic nucleotide-gated (CNG), non-selective cation channel which depolarizes the cells. Ca(2+) influx through the CNG channel in turn activates a Ca(2+)-activated Cl(-) channel, causing a Cl(-) efflux and further depolarization. In the absence of OMP, the time-to-transient-peak of the response, the latency to first spike, and the response termination were slowed 2- to 8-fold, indicating its role in regulating olfactory response kinetics and termination. This phenotype persisted in OMP(-/-) ORNs even in low external Ca(2+) solution chosen to prevent Cl(-) channel activation, suggesting OMP acts upstream of Cl(-) channel activation. Furthermore, the response kinetics in cilia are virtually indistinguishable between OMP(-/-) and wild-type ORNs when intracellular cAMP level was elevated by the phospho-diesterase inhibitor, IBMX, suggesting OMP acts upstream of cAMP production. Together, our results suggest a role for OMP in regulating the kinetics and termination of olfactory responses, implicating a novel mechanism for fast and robust response termination to ensure the temporal resolution of the odour stimulus. These observations also help explain the deficits in odour detection threshold and odour quality discrimination seen in the OMP(-/-) mice.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA. jreisert@monell.org
authors.forename: Johannes
authors.initials: J
authors.lastname: Reisert
authors.forename: King-Wai
authors.initials: KW
authors.lastname: Yau
authors.forename: Frank L
authors.initials: FL
authors.lastname: Margolis
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D002923:Cilia / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology*; D003511:Cyclohexanols / Q000494:pharmacology; D004594:Electrophysiology; D000077591:Eucalyptol; D005260:Female; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D039821:Monoterpenes / Q000494:pharmacology; D009812:Odorants; D051842:Olfactory Marker Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018034:Olfactory Receptor Neurons / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D012996:Solutions; D013268:Stimulation, Chemical
chemical_list: D003511:Cyclohexanols; D039821:Monoterpenes; D051842:Olfactory Marker Protein; D010726:Phosphodiesterase Inhibitors; D012996:Solutions; D000242:Cyclic AMP; D000077591:Eucalyptol