Seizure-induced plasticity of h channels in entorhinal cortical layer III pyramidal neurons

Neuron. 2004 Oct 28;44(3):495-508. doi: 10.1016/j.neuron.2004.10.011.

Abstract

The entorhinal cortex (EC) provides the predominant excitatory drive to the hippocampal CA1 and subicular neurons in chronic epilepsy. Discerning the mechanisms underlying signal integration within EC neurons is essential for understanding network excitability alterations involving the hippocampus during epilepsy. Twenty-four hours following a single seizure episode when there were no behavioral or electrographic seizures, we found enhanced spontaneous activity still present in the rat EC in vivo and in vitro. The increased excitability was accompanied by a profound reduction in I(h) in EC layer III neurons and a significant decline in HCN1 and HCN2 subunits that encode for h channels. Consequently, dendritic excitability was enhanced, resulting in increased neuronal firing despite hyperpolarized membrane potentials. The loss of I(h) and the increased neuronal excitability persisted for 1 week following seizures. Our results suggest that dendritic I(h) plays an important role in determining the excitability of EC layer III neurons and their associated neural networks.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Animals
  • Bicuculline / pharmacology
  • Blotting, Western / methods
  • Cyclic Nucleotide-Gated Cation Channels
  • Dendrites / drug effects
  • Dendrites / physiology
  • Electroencephalography / methods
  • Entorhinal Cortex / pathology*
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • GABA Antagonists / pharmacology
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Immunohistochemistry / methods
  • In Vitro Techniques
  • Ion Channels / antagonists & inhibitors
  • Ion Channels / physiology*
  • Kainic Acid
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Muscle Proteins / physiology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Patch-Clamp Techniques / methods
  • Potassium Channels
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiopathology*
  • Pyrimidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Seizures / chemically induced
  • Seizures / physiopathology*
  • Valine / analogs & derivatives*
  • Valine / pharmacology

Substances

  • Cyclic Nucleotide-Gated Cation Channels
  • Excitatory Amino Acid Agonists
  • GABA Antagonists
  • Hcn1 protein, rat
  • Hcn2 protein, rat
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels
  • Muscle Proteins
  • Potassium Channels
  • Pyrimidines
  • ICI D2788
  • 2-amino-5-phosphopentanoic acid
  • Valine
  • Kainic Acid
  • Bicuculline