Abstract
In olfactory receptor neurons (ORNs), ligand-odorant receptor interactions cause G protein-mediated activation of adenylate cyclase and a subsequent increase in concentration of the intracellular messenger cAMP. Odorant-evoked elevation in cAMP is thought to directly activate a cation-selective cyclic nucleotide-gated channel, which causes external Ca2+ influx, leading to membrane depolarization and the generation of action potentials. Our data show that in freshly dissociated rat ORNs, odorant-induced elevation in cAMP also activates cAMP-dependent protein kinase (PKA), which is then able to phosphorylate various protein targets in the olfactory signal transduction pathway, specifically voltage-gated sodium and calcium channels. The presence of PKI (PKA inhibitor peptide) blocked the modulatory action of cAMP on voltage-gated ion channels. By modulating the input/output properties of the sensory neurons, this mechanism could take part in the complex adaptation process in odorant perception. In addition, we found modulation of voltage-gated sodium and calcium channel currents by 5-hydroxytryptamine and the dopamine D1 receptor agonist SKF 38393. These findings suggest that in situ ORNs might also be a target for efferent modulation.
MeSH terms
-
Animals
-
Barium / pharmacology
-
Calcium Channels / drug effects
-
Calcium Channels / metabolism
-
Cells, Cultured / cytology
-
Cells, Cultured / drug effects
-
Cells, Cultured / metabolism
-
Colforsin / pharmacology
-
Cyclic AMP / metabolism*
-
Cyclic AMP-Dependent Protein Kinases / metabolism*
-
Enzyme Inhibitors / pharmacology
-
Ion Channels / drug effects
-
Ion Channels / metabolism*
-
Male
-
Membrane Potentials / drug effects
-
Membrane Potentials / physiology
-
Neurotransmitter Agents / metabolism
-
Neurotransmitter Agents / pharmacology
-
Odorants
-
Olfactory Receptor Neurons / cytology
-
Olfactory Receptor Neurons / drug effects
-
Olfactory Receptor Neurons / metabolism*
-
Patch-Clamp Techniques
-
Peptides / pharmacology
-
Phosphorylation / drug effects
-
Rats
-
Rats, Wistar
-
Receptors, Neurotransmitter / drug effects
-
Receptors, Neurotransmitter / metabolism
-
Receptors, Odorant / drug effects
-
Receptors, Odorant / metabolism*
-
Signal Transduction / drug effects
-
Signal Transduction / physiology*
-
Smell / drug effects
-
Smell / physiology*
-
Sodium Channels / drug effects
-
Sodium Channels / metabolism
Substances
-
Calcium Channels
-
Enzyme Inhibitors
-
Ion Channels
-
Neurotransmitter Agents
-
Peptides
-
Receptors, Neurotransmitter
-
Receptors, Odorant
-
Sodium Channels
-
protein kinase inhibitor peptide
-
Colforsin
-
Barium
-
Cyclic AMP
-
Cyclic AMP-Dependent Protein Kinases