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 i ncrease in concentration of the intracellular messenger cAMP. Odorant-evoke d elevation in cAMP is thought to directly activate a cation-selective cycl ic nucleotide-gated channel, which causes external Ca2+ influx, leading to membrane depolarization and the generation of action potentials. Our data s how 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 presen ce of PKI (PKA inhibitor peptide) blocked the modulatory action of cAMP on voltage-gated ion channels. By modulating the input/output properties of th e 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 d opamine D-1 receptor agonist SKF 38393. These findings suggest that in situ ORNs might also be a target for efferent modulation.