title: Persistent ictal-like activity in rat entorhinal/perirhinal cortex following washout of 4-aminopyridine.
abstract: Application of 4-aminopyridine (4-AP, 100μM) in a solution containing 0.6mM Mg(2+) and 1.2mM Ca(2+) to hippocampal-entorhinal-perirhinal slices of adult rat brain induced ictal-like epileptiform activity in entorhinal and perirhinal cortices as revealed by electrophysiological field potential recordings. The ictal-like activity persisted after washing out the 4-AP. This persistence indicated that a change had occurred in the slice so that it was now "epileptic" in the absence of the convulsant 4-AP. Induction of persistent ictal-like activity was dependent upon the concentration of divalent cations during 4-AP exposure; that is, although 4-AP caused ictal-like activity in approximately half the slices in solution containing 1.6mM Mg(2+) and 2.0mM Ca(2+), this ictal-like activity did not persist upon washout of the 4-AP. Expression of the persistent ictal-like epileptiform activity required ionotropic glutamate-mediated synaptic transmission: application of the AMPA/kainate receptor antagonist NBQX after 4-AP washout reduced persistent ictal-like activity, and the combined application of NBQX and the NMDA receptor antagonist d-AP5 completely blocked it. In order to investigate the mechanism of induction of persistent ictal-like activity, several agents were applied before the introduction of 4-AP. Application of d-AP5 did not block the onset of ictal-like activity upon introduction of 4-AP but did prevent the persistence of the ictal-like activity upon washout of the 4-AP. In contrast, induction of persistent ictal-like activity was not prevented by simultaneous application of the group I metabotropic glutamate receptor (mGluR) antagonists LY 367385 and MPEP or by application of the protein synthesis inhibitor cycloheximide. In conclusion, we have characterized a new in vitro model of epileptogenesis in which induction of ictal-like activity is dependent upon NMDA receptor activation but not upon group I mGluR activation or protein synthesis.
authors.affiliation: Program in Neural and Behavioral Science, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, United States.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Salah
authors.affiliation: Program in Neural and Behavioral Science, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, United States; Department of Physiology and Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, United States; Robert F. Furchgott Center for Neural and Behavioral Science, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, United States.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Perkins
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004594:Electrophysiology; D018728:Entorhinal Cortex / Q000187:drug effects*; D005071:Evoked Potentials / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018691:Excitatory Amino Acid Antagonists; D026902:Potassium Channel Blockers; D011500:Protein Synthesis Inhibitors; D003513:Cycloheximide; D015761:4-Aminopyridine; D008274:Magnesium; D002118:Calcium