Epileptiform discharge induced by 4-aminopyridine in magnesium-free medium in neocortical neurons: Physiological and pharmacological characterization

A. Siniscalchi, P. Calabresi, N. B. Mercuri, G. Bernardi

Research output: Contribution to journalArticlepeer-review

Abstract

An in vitro model of epileptiform activity was developed to study the role of excitatory and inhibitory neurotransmitters in the epileptogenesis. Intracellular recordings were obtained from rat neocortical slices exposed to 4-aminopyridine in a magnesium-free solution. Spontaneous epileptiform activity consisting of paroxysmal depolarization shifts with associated spontaneous depolarizing postsynaptic potentials were observed. The paroxysmal depolarization shifts were blocked either by D,L-2-amino-5- phosphonovalerate (50 μM), an N-methyl-D-aspartate receptor antagonist, or by 6-cyano-7-nitroquinoxaline-2.3-dione (10 μM), a non-N-methyl-D-aspartate receptor antagonist. These glutamate receptor antagonists also reduced the occurrence of spontaneous depolarizing postsynaptic potentials. Bicuculline methiodide, an antagonist of GABA(A) receptors, suppressed spontaneous depolarizing postsynaptic potentials, while it reduced the frequency of paroxysmal depolarization shifts and increased their duration. Hyperpolarization of the membrane potential by continuous current injection increased the frequency of paroxysmal depolarization shifts and reduced their duration, but it reduced the occurrence of spontaneous postsynaptic potentials. Paroxysmal depolarization shifts were blocked by tetrodotoxin (1 μM). The duration and the frequency of paroxysmal depolarization shift were reduced by dopamine (30-300 μM) in a dose-dependent manner. Our model suggests a different involvement of excitatory and inhibitory processes in the generation of epileptiform activity.

Original languageEnglish
Pages (from-to)189-197
Number of pages9
JournalNeuroscience
Volume81
Issue number1
DOIs
Publication statusPublished - Aug 26 1997

Keywords

  • Epilepsy
  • Excitatory amino acids
  • GABA
  • Neocortex
  • Paroxysmal depolarization shift

ASJC Scopus subject areas

  • Neuroscience(all)

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