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Regulation of voltage-dependent calcium channels in rat sensory neurones involves a Ras-mitogen-activated protein

E M Fitzgerald1

  • 1Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. e.fitzgerald@ucl.ac.uk

The Journal of Physiology
|September 16, 2000
PubMed

Insights

The Ras-MAPK pathway enhances voltage-dependent calcium channels (VDCCs) in rat sensory neurons. This pathway, specifically Raf-1 activation, is crucial for regulating calcium currents, independent of gene expression.

Area of Science:

  • Neuroscience
  • Cellular Biology
  • Molecular Biology

Background:

  • The small G-protein Ras is vital for cell growth signaling.
  • Ras influences voltage-dependent calcium channels (VDCCs) in rat sensory neurons.
  • Downstream effectors of Ras in this process require identification.

Purpose of the Study:

  • To determine which Ras downstream effectors modulate VDCCs in rat sensory neurons.
  • To elucidate the specific pathway involved in Ras-mediated calcium current regulation.

Main Methods:

  • Co-expression of Ras mutant cDNAs with GFP in cultured rat dorsal root ganglion neurons (DRGs).
  • Measurement of basal calcium current density using electrophysiology.
  • Application of MEK inhibitor U0126 to assess pathway involvement.

Main Results:

  • Constitutively active V12Ras increased calcium current density by 41%.
  • V12S35Ras, activating Raf-1 and MAPK, increased current density by 67%.
  • MEK inhibition rapidly reduced calcium current, indicating direct modulation via the Ras-MAPK pathway.

Conclusions:

  • Ras-mediated enhancement of VDCCs in DRGs is sufficient via Raf-1 activation.
  • The Ras-MAPK pathway directly modulates VDCCs, not through gene expression.
  • Both N-type and L-type calcium currents in DRGs are enhanced by this pathway.

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