title: Cyclic AMP cascade mediates the inhibitory odor response of isolated toad olfactory receptor neurons.
abstract: Odor stimulation may excite or inhibit olfactory receptor neurons (ORNs). It is well established that the excitatory response involves a cyclic AMP (cAMP) transduction mechanism that activates a nonselective cationic cyclic nucleotide-gated (CNG) conductance, accompanied by the activation of a Ca2+-dependent Cl(-) conductance, both causing a depolarizing receptor potential. In contrast, odor inhibition is attributed to a hyperpolarizing receptor potential. It has been proposed that a Ca2+-dependent K+ (K(Ca)) conductance plays a key role in odor inhibition, both in toad and rat isolated olfactory neurons. The mechanism underlying odor inhibition has remained elusive. We assessed its study using various pharmacological agents and caged compounds for cAMP, Ca2+, and inositol 1,4,5-triphosphate (InsP3) on isolated toad ORNs. The odor-triggered K(Ca) current was reduced on exposing the cell either to the CNG channel blocker LY83583 (20 microM) or to the adenylyl cyclase inhibitor SQ22536 (100 microM). Photorelease of caged Ca2+ activated a Cl- current sensitive to niflumic acid (10 microM) and a K+ current blockable by charybdotoxin (20 nM) and iberiotoxin (20 nM). In contrast, photoreleased Ca2+ had no effect on cells missing their cilia, indicating that these conductances are confined to the cilia. Photorelease of cAMP induced a charybdotoxin-sensitive K+ current in intact ORNs. Photorelease of InsP3 did not increase the membrane conductance of olfactory neurons, arguing against a direct role of InsP3 in chemotransduction. We conclude that a cAMP cascade mediates the activation of the ciliary Ca2+-dependent K+ current and that the Ca2+ ions that activate the inhibitory current enter the cilia through CNG channels.
authors.affiliation: Department of Biology, Faculty of Sciences, University of Chile, P.O. Box 653, Santiago, Chile.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Madrid
authors.forename: Ricardo
authors.initials: R
authors.lastname: Delgado
authors.forename: Juan
authors.initials: J
authors.lastname: Bacigalupo
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001001:Anura; D002103:Cadaverine / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D045424:Complex Mixtures / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008959:Models, Neurological; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D009812:Odorants; D018034:Olfactory Receptor Neurons / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D015398:Signal Transduction / Q000502:physiology; D014466:Ultraviolet Rays
chemical_list: C089981:(2-nitrophenyl)ethyl-cyclic adenosine monophosphate; D000634:Aminoquinolines; D045424:Complex Mixtures; D004791:Enzyme Inhibitors; D018999:Charybdotoxin; C017759:9-(tetrahydro-2-furyl)-adenine; C041715:6-anilino-5,8-quinolinedione; D000242:Cyclic AMP; D000225:Adenine; D002103:Cadaverine