Voltage-gated channels block nicotinic regulation of CREB phosphorylation and gene expression in neurons

Neuron. 2001 Dec 6;32(5):855-65. doi: 10.1016/s0896-6273(01)00516-5.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium Channels, L-Type / metabolism*
  • Cells, Cultured
  • Chick Embryo
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nicotine / pharmacology
  • Nicotinic Agonists / pharmacology
  • Phosphorylation / drug effects
  • Receptors, Nicotinic / physiology*
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / metabolism
  • Transcription Factors / metabolism


  • Calcium Channels, L-Type
  • Cyclic AMP Response Element-Binding Protein
  • Nicotinic Agonists
  • Receptors, Nicotinic
  • Transcription Factors
  • Nicotine