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Growth factors differentially regulate neuronal Cav channels via ERK-dependent signalling

A J Woodall1, M A Richards, D J Turner

  • 1Faculty of Life Sciences, The University of Manchester, Manchester M13 9NT, UK.

Cell Calcium
|November 13, 2007
PubMed

Insights

Neurotrophic factors like NGF, GDNF, and EGF regulate voltage-gated calcium channels (Ca(v)) via ERK signaling in sensory neurons. These factors fine-tune calcium influx through distinct mechanisms, impacting neuronal function.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Signaling

Background:

  • Voltage-gated calcium channels (Ca(v)) are crucial for neuronal function and are regulated by Ras/extracellular signal-regulated kinase (ERK) signaling.
  • The precise mechanisms controlling the specificity of cellular responses to ERK signaling in neurons are not fully understood.
  • Neurotrophic factors are known regulators of ERK signaling and play vital roles in neuronal survival, development, and plasticity.

Purpose of the Study:

  • To investigate the role of endogenous neurotrophic factors (NGF, GDNF, EGF) in the tonic, ERK-dependent regulation of Ca(v) channels in rat dorsal root ganglion neurons.
  • To elucidate the distinct mechanisms and time-frames through which these growth factors modulate Ca(v) channel activity.
  • To determine if NGF, GDNF, and EGF differentially regulate specific Ca(v) channel populations.

Main Methods:

  • Utilized rat dorsal root ganglion neurons.
  • Employed chronic deprivation of growth factors to assess effects on Ca(v) currents.
  • Investigated both transcriptional and acute modulatory effects of growth factors on Ca(v) channels.
  • Analyzed changes in Ca(v) channel gating and surface expression.

Main Results:

  • Endogenous NGF, GDNF, and EGF contribute to tonic ERK-dependent up-regulation of Ca(v) channels.
  • Growth factor deprivation altered Ca(v) currents, correlating with changes in receptor expression.
  • EGF specifically regulated Ca(v) transcriptional expression, while NGF and GDNF induced rapid, acute modulation of Ca(v) channels (within ~10 min) likely via altered gating.
  • NGF, GDNF, and EGF demonstrated differential regulation of specific Ca(v) channel populations.

Conclusions:

  • Neurotrophic factors NGF, GDNF, and EGF are key players in the ERK-dependent regulation of Ca(v) channels in sensory neurons.
  • These factors offer a flexible system for tailoring calcium influx through both transcriptional and rapid post-translational mechanisms.
  • The differential regulation of Ca(v) channels by these factors allows for precise control of neuronal excitability and function.

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