Enhancement of N- and L-type calcium channel currents by protein kinase C in frog sympathetic neurons

Neuron. 1993 Feb;10(2):127-36. doi: 10.1016/0896-6273(93)90305-b.

Abstract

The effect of protein kinase C (PKC) stimulation on Ca2+ channels was studied in frog sympathetic neurons. 12,13-Phorbol dibutyrate (PDBu) consistently augmented Ca2+ channel currents in whole-cell recordings. This enhancement was blocked by staurosporine and PKC(19-31), but not produced by 4 alpha-phorbol 12,13-didecanoate, indicating that PDBu acts via PKC. Both N- and L-type currents, as isolated pharmacologically, were increased. PKC enhancement was independent of the extent of G protein activation, indicating that it was not caused by removal of tonic G protein inhibition. In unitary recordings PDBu produced dramatic increases in single N- and L-type channel activity by sharply decreasing closed time intervals between adjacent openings, but did not alter the unitary current size or mean open time. This up-modulation by PKC may constitute a positive feedback mechanism in the regulation of neuronal Ca2+ channel activity.

Publication types

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

MeSH terms

  • Alkaloids / pharmacology
  • Animals
  • Barium / metabolism
  • Calcium Channels / physiology*
  • Electric Conductivity
  • GTP-Binding Proteins / physiology
  • Ganglia, Sympathetic / physiology*
  • Kinetics
  • Neurons / physiology*
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Phorbol Esters / pharmacology
  • Protein Kinase C / pharmacology*
  • Rana catesbeiana
  • Staurosporine

Substances

  • Alkaloids
  • Calcium Channels
  • Phorbol Esters
  • phorbol-12,13-didecanoate
  • Barium
  • Phorbol 12,13-Dibutyrate
  • Protein Kinase C
  • GTP-Binding Proteins
  • Staurosporine