title: Voltage-gated channels block nicotinic regulation of CREB phosphorylation and gene expression in neurons.
abstract: Synaptic activation of the transcription factor CREB and downstream gene expression usually depend on calcium influx aided by voltage-gated calcium channels. We find that nicotinic signaling, in contrast, activates CREB and gene expression in ciliary ganglion neurons both in culture and in situ only if voltage-gated channels are silent. The nicotinic response requires calcium influx and release from internal stores and acts through CaMK and MAPK pathways to sustain activated CREB. Voltage-gated channels mobilize CaMK to activate CREB initially, but they also enable calcineurin and PP1 to terminate the activation before transcription is affected. L-type voltage-gated channels dominate the outcome and block the effects of nicotinic signaling on transcription. This demonstrates a novel aspect of activity-dependent gene regulation.
authors.affiliation: Neurobiology Section, Division of Biology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: K T
authors.initials: KT
authors.lastname: Chang
authors.forename: D K
authors.initials: DK
authors.lastname: Berg
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D017362:Cyclic AMP Response Element-Binding Protein; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D014157:Transcription Factors; D009538:Nicotine