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Olfactory marker protein directly buffers cAMP to avoid depolarization-induced silencing of olfactory receptor neurons
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Olfactory marker protein directly buffers cAMP to avoid depolarization-induced silencing of olfactory receptor neurons
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Journal Article
Olfactory marker protein directly buffers cAMP to avoid depolarization-induced silencing of olfactory receptor neurons
2020
Overview
Olfactory receptor neurons (ORNs) use odour-induced intracellular cAMP surge to gate cyclic nucleotide-gated nonselective cation (CNG) channels in cilia. Prolonged exposure to cAMP causes calmodulin-dependent feedback-adaptation of CNG channels and attenuates neural responses. On the other hand, the odour-source searching behaviour requires ORNs to be sensitive to odours when approaching targets. How ORNs accommodate these conflicting aspects of cAMP responses remains unknown. Here, we discover that olfactory marker protein (OMP) is a major cAMP buffer that maintains the sensitivity of ORNs. Upon the application of sensory stimuli, OMP directly captured and swiftly reduced freely available cAMP, which transiently uncoupled downstream CNG channel activity and prevented persistent depolarization. Under repetitive stimulation,
OMP
-/-
ORNs were immediately silenced after burst firing due to sustained depolarization and inactivated firing machinery. Consequently,
OMP
-/-
mice showed serious impairment in odour-source searching tasks. Therefore, cAMP buffering by OMP maintains the resilient firing of ORNs.
The physiological role of the olfactory marker protein (OMP) has been elusive. Here, the authors demonstrate that OMP buffers cAMP and modulates cAMP-gated channel activity upon sensory stimulation, maintaining neuronal firing during odour-source searching.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/44
/ 13/51
/ 14
/ 14/33
/ 14/5
/ 38
/ 64
/ 64/60
/ 9/74
/ 9/97
/ Animals
/ Buffers
/ Channels
/ Cilia
/ Cyclic Nucleotide-Gated Cation Channels - metabolism
/ Humanities and Social Sciences
/ Humans
/ Ion channels (cyclic nucleotide-gated)
/ Ions
/ Male
/ Markers
/ Membrane Potentials - drug effects
/ Neurons
/ Odorants
/ Odors
/ Olfactory Marker Protein - genetics
/ Olfactory Marker Protein - metabolism
/ Olfactory Mucosa - drug effects
/ Olfactory Mucosa - physiology
/ Olfactory Receptor Neurons - cytology
/ Olfactory Receptor Neurons - metabolism
/ Olfactory Receptor Neurons - physiology
/ Proteins
/ Science
