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Profiling Voltage-gated Potassium Channel mRNA Expression in Nigral Neurons using Single-cell RT-PCR Techniques
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Voltage-gated channels block nicotinic regulation of CREB phosphorylation and gene expression in neurons

K T Chang1, D K Berg

  • 1Neurobiology Section, Division of Biology, University of California, San Diego, La Jolla, CA 92093, USA.

Neuron
|December 12, 2001
PubMed

Insights

Nicotinic signaling activates CREB and gene expression in neurons, but only when voltage-gated calcium channels are inactive. These channels normally block this pathway, highlighting a new form of activity-dependent gene regulation.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cellular Signaling

Background:

  • Synaptic activation of CREB (cAMP response element-binding protein) and gene expression typically relies on calcium influx via voltage-gated calcium channels.
  • Understanding the regulation of CREB activation is crucial for deciphering neuronal plasticity and function.

Purpose of the Study:

  • To investigate the role of nicotinic signaling in CREB activation and gene expression in ciliary ganglion neurons.
  • To determine the interplay between nicotinic signaling and voltage-gated calcium channels in regulating CREB activity.

Main Methods:

  • Experiments were conducted on ciliary ganglion neurons both in culture and in situ.
  • Investigated calcium influx, release from internal stores, and the involvement of CaMK and MAPK pathways.
  • Manipulated voltage-gated calcium channel activity to assess its impact on nicotinic signaling pathways.

Main Results:

  • Nicotinic signaling activates CREB and gene expression independently of voltage-gated calcium channels when these channels are silent.
  • The nicotinic pathway requires calcium influx and release from internal stores, engaging CaMK and MAPK.
  • Voltage-gated calcium channels initially activate CREB but also trigger calcineurin and PP1 to terminate activation, thereby blocking nicotinic effects on transcription, particularly L-type channels.

Conclusions:

  • Nicotinic signaling provides an alternative pathway for CREB activation and gene expression in neurons.
  • Voltage-gated calcium channels act as a gatekeeper, inhibiting nicotinic-driven transcription by promoting CREB deactivation.
  • This study reveals a novel mechanism of activity-dependent gene regulation distinct from canonical pathways.

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