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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Calcium Channels, L-Type / metabolism*
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Cells, Cultured
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Chick Embryo
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Cyclic AMP Response Element-Binding Protein / metabolism*
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Dose-Response Relationship, Drug
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Electric Stimulation
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Female
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology*
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Ion Channel Gating / drug effects
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Ion Channel Gating / physiology*
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Neurons / drug effects
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Neurons / metabolism*
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Nicotine / pharmacology
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Nicotinic Agonists / pharmacology
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Phosphorylation / drug effects
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Receptors, Nicotinic / physiology*
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Retinal Ganglion Cells / drug effects
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Retinal Ganglion Cells / metabolism
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Transcription Factors / metabolism
Substances
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Calcium Channels, L-Type
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Cyclic AMP Response Element-Binding Protein
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Nicotinic Agonists
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Receptors, Nicotinic
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Transcription Factors
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Nicotine