Voltage-gated channels block nicotinic regulation of CREB phosphorylation and gene expression in neurons.
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.
Chang
K T
KT
Neurobiology Section, Division of Biology, University of California, San Diego, La Jolla, CA 92093, USA.
Berg
D K
DK
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
D020746:Calcium Channels, L-Type; D017362:Cyclic AMP Response Element-Binding Protein; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D014157:Transcription Factors; D009538:Nicotine