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Published on: January 23, 2012

Modulation of N-type calcium channel activity by G-proteins and protein kinase C

C F Barrett1, A R Rittenhouse

  • 1Program in Molecular Physiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.

The Journal of General Physiology
|February 29, 2000
PubMed

Insights

Protein kinase C (PKC) phosphorylation prevents G-protein inhibition of N-type calcium channels. However, PKC phosphorylation does not affect other channel functions when G-protein activity is minimized.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Ion Channel Physiology

Background:

  • N-type voltage-gated calcium channels are crucial for neuronal function.
  • These channels are modulated by G-proteins and protein kinase C (PKC).
  • Distinct pathways suggest convergence on the alpha(1B) subunit, potentially leading to mutual exclusivity.

Purpose of the Study:

  • To investigate the interaction between G-protein-mediated inhibition and PKC phosphorylation on N-type calcium channels.
  • To determine if PKC phosphorylation affects other channel properties beyond antagonizing G-protein inhibition.

Main Methods:

  • Whole-cell barium currents were recorded in neonatal rat superior cervical ganglion neurons.
  • G-proteins were activated using GTP or GTP-gamma-S.
  • PKC was activated using phorbol 12-myristate 13-acetate (PMA).
  • GDP-beta-S was used to minimize G-protein activation.

Main Results:

  • PKC-induced reversal of G-protein inhibition required prior G-protein dissociation.
  • PKC phosphorylation rendered channels resistant to subsequent G-protein inhibition.
  • PKC phosphorylation did not affect peak current, inactivation, or activation when G-protein effects were minimized.

Conclusions:

  • PKC phosphorylation primarily acts to prevent G-protein-mediated inhibition of N-type calcium channels.
  • Under conditions minimizing G-protein activity, PKC phosphorylation has no independent effect on N-type channel function.

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