Abstract
In the nose, odorants are detected on the cilia of olfactory sensory neurons (OSNs), where a cAMP-mediated signaling pathway transforms odor stimulation into electrical responses. Phosphodiesterase (PDE) activity in OSN cilia has long been thought to account for rapid response termination by degrading odor-induced cAMP. Two PDEs with distinct cellular localization have been found in OSNs: PDE1C in the cilia and PDE4A throughout the cell but absent from the cilia. We disrupted both of these genes in mice and carried out electro-olfactogram analysis. Unexpectedly, eliminating PDE1C did not prolong response termination. Prolonged termination occurred only in mice that lacked both PDEs, suggesting that cAMP degradation by PDE1C in cilia is not a rate-limiting factor for response termination in wild-type mice. Pde1c(-/-) OSNs instead showed reduced sensitivity and attenuated adaptation to repeated stimulation, suggesting that PDE1C may be involved in regulating sensitivity and adaptation. Our observations provide new perspectives on the regulation of olfactory transduction.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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1-Methyl-3-isobutylxanthine / pharmacology
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Adaptation, Physiological / drug effects
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Adaptation, Physiological / genetics
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Animals
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Calcium / pharmacology
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Calmodulin / pharmacology
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Computer Simulation
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Cyclic AMP / metabolism
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Cyclic Nucleotide Phosphodiesterases, Type 1 / deficiency
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Cyclic Nucleotide Phosphodiesterases, Type 1 / metabolism*
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Cyclic Nucleotide Phosphodiesterases, Type 4 / deficiency
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Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism
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Dose-Response Relationship, Drug
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Evoked Potentials / drug effects
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Evoked Potentials / genetics
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Evoked Potentials / physiology*
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Mice
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Mice, Knockout
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Olfactory Mucosa / drug effects
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Olfactory Mucosa / metabolism
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Olfactory Receptor Neurons / drug effects
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Olfactory Receptor Neurons / physiology*
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Pentanols / pharmacology
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Phosphodiesterase Inhibitors / pharmacology
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Reaction Time / drug effects
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Reaction Time / genetics
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Reaction Time / physiology*
Substances
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Calmodulin
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Pentanols
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Phosphodiesterase Inhibitors
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amyl acetate
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Cyclic AMP
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Cyclic Nucleotide Phosphodiesterases, Type 1
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Pde1C protein, mouse
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Calcium
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1-Methyl-3-isobutylxanthine