Phosphorylation of voltage-gated ion channels in rat olfactory receptor neurons.
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.
Wetzel
C H
CH
Department of Cell Physiology, Ruhr-University Bochum, Universitaetsstrasse 150, 44780 Bochum, Germany.
Spehr
M
M
Hatt
H
H
D000818:Animals; D001464:Barium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000494:pharmacology; D009812:Odorants; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism; D018035:Receptors, Odorant / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012903:Smell / Q000187:drug effects / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D007473:Ion Channels; D018377:Neurotransmitter Agents; D010455:Peptides; D017981:Receptors, Neurotransmitter; D018035:Receptors, Odorant; D015222:Sodium Channels; C061479:protein kinase inhibitor peptide; D005576:Colforsin; D001464:Barium; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases