title: Retinoic acid affects calcium signaling in adult molluscan neurons.
abstract: Retinoic acid, the active metabolite of vitamin A, is important for nervous system development, regeneration, as well as cognitive functions of the adult central nervous system. These central nervous system functions are all highly dependent on neuronal activity. Retinoic acid has previously been shown to induce changes in the firing properties and action potential waveforms of adult molluscan neurons in a dose- and isomer-dependent manner. In this study, we aimed to determine the cellular pathways by which retinoic acid might exert such effects, by testing the involvement of pathways previously shown to be affected by retinoic acid. We demonstrated that the ability of all-trans retinoic acid (atRA) to induce electrophysiological changes in cultured molluscan neurons was not prevented by inhibitors of protein synthesis, protein kinase A or phospholipase C. However, we showed that atRA was capable of rapidly reducing intracellular calcium levels in the same dose- and isomer-dependent manner as shown previously for changes in neuronal firing. Moreover, we also demonstrated that the transmembrane ion flux through voltage-gated calcium channels was rapidly modulated by retinoic acid. In particular, the peak current density was reduced and the inactivation rate was increased in the presence of atRA, over a similar time course as the changes in cell firing and reductions in intracellular calcium. These studies provide further evidence for the ability of atRA to induce rapid effects in mature neurons.
authors.affiliation: Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Vesprini
authors.affiliation: Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada.
authors.forename: Taylor F
authors.initials: TF
authors.lastname: Dawson
authors.affiliation: Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada.
authors.forename: Doug
authors.initials: D
authors.lastname: Bruce
authors.affiliation: Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada gspencer@brocku.ca.
authors.forename: Gaynor E
authors.initials: GE
authors.lastname: Spencer
mesh_terms: D000200:Action Potentials; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008195:Lymnaea; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D061848:Optical Imaging; D018408:Patch-Clamp Techniques; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D018377:Neurotransmitter Agents; D047428:Protein Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; D001030:Apamin; D014212:Tretinoin; D017868:Cyclic AMP-Dependent Protein Kinases; D010738:Type C Phospholipases; D002118:Calcium
keywords: Lymnaea stagnalis; electrophysiology; protein synthesis; retinoid; second messengers; voltage-gated calcium channels