title: Nitric oxide potentiates cAMP-gated cation current in feeding neurons of Pleurobranchaea californica independent of cAMP and cGMP signaling pathways.
abstract: Critical roles for nitric oxide (NO) in regulating cell and tissue physiology are broadly appreciated, but aspects remain to be explored. In the mollusk Pleurobranchaea, NO synthase activity is high in CNS ganglia containing motor networks for feeding and locomotion, where a cAMP-gated cation current (I(Na,cAMP)) is also prominent in many neurons. We examined effects of NO on I(Na,cAMP) using voltage-clamp methods developed to analyze cAMP signaling in the live neuron, focusing on the identified metacerebral giant neuron of the feeding network. NO donors enhanced the I(Na,cAMP) response to injected cAMP by an averaged 85%. In dose-response measures, NO increased the current stimulated by cAMP injection without altering either apparent cAMP binding affinity or cooperativity of current activation. NO did not detectably alter levels of native cAMP or synthesis or degradation rates as observable in both current saturation and decay rate of I(Na,cAMP) responses to cAMP injection. NO actions were not exerted by cGMP signaling, as they were not mimicked by cGMP analogue nor blocked by inhibitors of guanylate cyclase and protein kinase G. NO potentiation of I(Na,cAMP) was broadly distributed among many other neurons of the feeding motor network in the buccal ganglion. However, NO did not affect a second type of I(Na,cAMP) found in locomotor neurons of the pedal ganglia. These results suggest that NO acts through a novel mechanism to regulate the gain of cAMP-dependent neuromodulatory pathways that activate I(Na,cAMP) and may thereby affect the set points of feeding network excitability and reactivity to exogenous input.
authors.affiliation: Deprtment of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 414 Burrill Hall, 407 S. Goodwin Ave., Urbana, IL 61801, USA.
authors.forename: Nathan G
authors.initials: NG
authors.lastname: Hatcher
authors.forename: Leland C
authors.initials: LC
authors.lastname: Sudlow
authors.forename: Leonid L
authors.initials: LL
authors.lastname: Moroz
authors.forename: Rhanor
authors.initials: R
authors.lastname: Gillette
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D004048:Diethylamines / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005247:Feeding Behavior / Q000502:physiology*; D017952:Ganglia, Invertebrate / Q000166:cytology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D049853:Pleurobranchaea; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors
chemical_list: C116907:1H-(1,2,4)oxadiazolo(4,3-a)-quiloxalin-1-one; D002227:Carbazoles; D004048:Diethylamines; D004791:Enzyme Inhibitors; D007211:Indoles; D010069:Oxadiazoles; D013873:Thionucleotides; C073601:KT 5823; C083763:8-bromoguanosino-3',5'-cyclic monophosphorothioate; D009569:Nitric Oxide; C034281:diethylamine; D006152:Cyclic GMP