Muscarinic modulation of sodium current by activation of protein kinase C in rat hippocampal neurons

Neuron. 1996 May;16(5):1019-26. doi: 10.1016/s0896-6273(00)80125-7.


Phosphorylation of brain Na+ channels by protein kinase C (PKC) decreases peak Na+ current and slows macroscopic inactivation, but receptor-activated modulation of Na+ currents via the PKC pathway has not been demonstrated. We have examined modulation of Na+ channels by activation of muscarinic receptors in acutely-isolated hippocampal neurons using whole-cell voltage-clamp recording. Application of the muscarinic agonist carbachol reduced peak Na+ current and slowed macroscopic inactivation at all potentials, without changing the voltage-dependent properties of the channel. These effects were mediated by PKC, since they were eliminated when the specific PKC inhibitor (PKCI19-36) was included in the pipette solution and mimicked by the extracellular application of the PKC activator, OAG. Thus, activation of endogenous muscarinic receptors on hippocampal neurons strongly modulates Na+ channel activity by activation of PKC. Cholinergic input from basal forebrain neurons may have this effect in the hippocampus in vivo.

Publication types

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

MeSH terms

  • Animals
  • Carbachol / pharmacology
  • Enzyme Activation
  • Hippocampus / physiology*
  • Ion Channel Gating*
  • Male
  • Phosphorylation
  • Protein Kinase C / physiology*
  • Rats
  • Receptors, Muscarinic / physiology*
  • Sodium / physiology
  • Sodium Channels / physiology*


  • Receptors, Muscarinic
  • Sodium Channels
  • Carbachol
  • Sodium
  • Protein Kinase C