Muscarinic modulation of sodium current by activation of protein kinase C in rat hippocampal neurons.
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.
Cantrell
A R
AR
Department of Pharmacology, University of Washington, Seattle, 98195-7280, USA.
Ma
J Y
JY
Scheuer
T
T
Catterall
W A
WA
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004789:Enzyme Activation; D006624:Hippocampus / Q000502:physiology*; D015640:Ion Channel Gating; D008297:Male; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000502:physiology*; D012964:Sodium / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology*
D011976:Receptors, Muscarinic; D015222:Sodium Channels; D002217:Carbachol; D012964:Sodium; D011493:Protein Kinase C