Protein kinase C modulates glutamate receptor inhibition of Ca2+ channels and synaptic transmission

Nature. 1993 Jan 14;361(6408):165-8. doi: 10.1038/361165a0.


Fast synaptic transmission in the central nervous system can be modulated by neurotransmitters and second-messenger pathways. For example, transmission at glutamatergic synapses can be depressed by the metabotropic glutamate receptor, providing autoreceptor-mediated negative feedback. Metabotropic glutamate receptor inhibition of Ca2+ channels may contribute to this pathway. In contrast, stimulation of protein kinase C can enhance excitatory synaptic transmission, whereas both depression and enhancement of Ca2+ current have been reported. Here we show that in hippocampal CA3 and cortical pyramidal neurons, activation of protein kinase C enhances current through N-type Ca2+ channels and, in addition, dramatically reduces G protein-dependent inhibition of these same channels by the metabotropic glutamate receptor. In parallel experiments on fast excitatory transmission at corticostriatal synapses, kinase C activators were similarly found to reduce the inhibitory effect produced by stimulation of the metabotropic glutamate receptor. The results show that second-to-second control of Ca2+ channels by the metabotropic glutamate receptor can itself be modulated on a slower timescale by protein kinase C. These mechanisms may be used in the control of fast excitatory synaptic transmission.

Publication types

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

MeSH terms

  • Animals
  • Calcium Channels / drug effects
  • Calcium Channels / physiology*
  • Cyclopentanes / pharmacology
  • Dimethyl Sulfoxide / pharmacology
  • Enzyme Activation
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Kinetics
  • Membrane Potentials / drug effects
  • Neurons / drug effects
  • Neurons / physiology*
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Protein Kinase C / metabolism*
  • Pyramidal Tracts / drug effects
  • Pyramidal Tracts / physiology*
  • Rats
  • Receptors, Glutamate / drug effects
  • Receptors, Glutamate / physiology*
  • Synapses / drug effects
  • Synapses / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • gamma-Aminobutyric Acid / physiology


  • Calcium Channels
  • Cyclopentanes
  • Receptors, Glutamate
  • Phorbol 12,13-Dibutyrate
  • gamma-Aminobutyric Acid
  • 3-aminocyclopentane-1-carboxylic acid
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate
  • Dimethyl Sulfoxide