Inhibitory odorant signaling in Mammalian olfactory receptor neurons
Kirill Ukhanov1, Elizabeth A Corey, Daniela Brunert
1Whitney Laboratory, Center for Smell and Taste, University of Florida, Gainesville, FL 32610-0127, USA. ukhanov@mbi.ufl.edu
Abstract:
Odorants inhibit as well as excite olfactory receptor neurons (ORNs) in many species of animals. Cyclic nucleotide-dependent activation of canonical mammalian ORNs is well established but it is still unclear how odorants inhibit these cells. Here we further implicate phosphoinositide-3-kinase (PI3K), an indispensable element of PI signaling in many cellular processes, in olfactory transduction in rodent ORNs. We show that odorants rapidly and transiently activate PI3K in the olfactory cilia and in the olfactory epithelium in vitro. We implicate known G-protein-coupled isoforms of PI3K and show that they modulate not only the magnitude but also the onset kinetics of the electrophysiological response of ORNs to complex odorants. Finally, we show that the ability of a single odorant to inhibit another can be PI3K dependent. Our collective results provide compelling support for the idea that PI3K-dependent signaling mediates inhibitory odorant input to mammalian ORNs and at least in part contributes to the mixture suppression typically seen in the response of ORNs to complex natural odorants.
Insights
Phosphoinositide-3-kinase (PI3K) mediates inhibitory odorant signals in mammalian olfactory receptor neurons (ORNs). This PI3K-dependent signaling also contributes to mixture suppression in responses to natural odorants.
Area of Science:
- Neuroscience
- Olfactory Signaling
- Molecular Biology
Background:
- Olfactory receptor neurons (ORNs) exhibit both excitatory and inhibitory responses to odorants.
- While excitatory pathways involving cyclic nucleotides are understood, the mechanisms of odorant-induced inhibition in ORNs remain unclear.
- Phosphoinositide-3-kinase (PI3K) is a key signaling molecule in various cellular processes.
Purpose of the Study:
- To investigate the role of PI3K in mediating inhibitory olfactory transduction in rodent ORNs.
- To determine if PI3K activation by odorants affects the electrophysiological responses of ORNs.
- To explore PI3K's contribution to odorant mixture suppression.
Main Methods:
- Measurement of PI3K activation in olfactory cilia and epithelium in vitro upon odorant stimulation.
- Identification of G-protein-coupled PI3K isoforms involved in olfactory transduction.
- Electrophysiological recordings of ORN responses to assess modulation of magnitude and kinetics.
Main Results:
- Odorants were shown to rapidly and transiently activate PI3K in rodent olfactory cilia and epithelium.
- Specific G-protein-coupled PI3K isoforms were implicated in modulating ORN response magnitude and onset kinetics.
- The inhibitory effect of one odorant on another was demonstrated to be PI3K-dependent.
Conclusions:
- PI3K-dependent signaling pathways mediate inhibitory odorant input to mammalian ORNs.
- PI3K plays a significant role in odorant mixture suppression observed in natural odorant responses.
- This study provides compelling evidence for PI3K's involvement in the complexity of olfactory processing.
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