Cholinergic-dependent Plateau Potential in Hippocampal CA1 Pyramidal Neurons

J Neurosci. 1996 Jul 1;16(13):4113-28. doi: 10.1523/JNEUROSCI.16-13-04113.1996.

Abstract

Cholinergic stimulation of the hippocampal formation results in excitation and/or seizure. We report here, using whole-cell patch-clamp techniques in the hippocampal slice (34-35 degrees C), a cholinergic-dependent slow afterdepolarization (sADP) and long-lasting plateau potential (PP). In the presence of 20 microM carbachol, action potential firing evoked by weak intracellular current injection elicited an sADP that lasted several seconds. Increased spike firing evoked by stronger depolarizing stimuli resulted in long-duration PPs maintained close to -20 mV. Removal of either Na+ or Ca2+ from the external media, intracellular Ca2+ ([Ca2+]i) chelation with 10 mM bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid, or the addition of 100 microM Cd2+ to the perfusate abolished both the sADP and PP. The sADP was depressed and the PP was abolished by either 10 microM nimodipine or 1 microM omega-conotoxin, whereas 1.2 microM tetrodotoxin was ineffective. The involvement of a Na+/Ca2+ exchanger was minimal because both the sADP and PP persisted after equimolar substitution of 50 mM Li+ for Na+ in the external media or reduction of the bath temperature to 25 degrees C. Finally in the absence of carbachol the sADP and PP could not be evoked when K+ channels were suppressed, suggesting that depression of K+ conductances alone was not sufficient to unmask the conductance. Based on these data, we propose that a Ca2+-activated nonselective cation conductance was directly enhanced by muscarinic stimulation. The sADP, therefore, represents activation of this conductance by residual [Ca2+]i, whereas the PP represents a novel regenerative event involving the interplay between high-voltage-activated Ca2+ channels and the Ca2+-activated nonselective cation conductance. This latter mechanism may contribute significantly to ictal depolarizations observed during cholinergic-induced seizures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbachol / pharmacology
  • Cholinergic Agents / pharmacology*
  • Electric Conductivity
  • Electrophysiology
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Ions
  • Neurons / drug effects*
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Potassium Channel Blockers
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Cholinergic Agents
  • Ions
  • Potassium Channel Blockers
  • Carbachol