Epileptiform discharges and a synchronous GABAergic potential induced by 4-aminopyridine in the rat immature hippocampus.
Extracellular field potential recordings were performed in the CA3 subfield of hippocampal slices that were obtained from 10- to 30-day-old rats. During perfusion with medium containing the convulsant drug 4-aminopyridine (4-AP, 50 microM) 3 main types of spontaneously occurring potentials were observed. The first one was a short-lasting (duration: 400-1100 ms) potential with a frequency of occurrence that ranged between 0.6 and 1.3 Hz. Thus it resembled an epileptiform interictal event. The second type was reminiscent of an ictal epileptiform discharge, lasted 10-35 s and recurred every 40-100 s. The third one was of opposite polarity as compared with the other two types, occurred every 10-100 s and was often followed by the ictal discharge. When recorded in isolation this potential lasted 1.2-2 s. The interictal and ictal discharges were blocked by the non-N-methyl-D-aspartate (non-NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM), while the potential of opposite polarity was not affected by this pharmacological procedure. It was, however, blocked in a reversible way by the GABAA receptor antagonist bicuculline methiodide (5 microM). These results indicate that in addition to epileptiform activity of interictal and ictal type, 4-AP also induces in the immature rat hippocampus a synchronous event that is due to the activation of the GABAA receptor.
Avoli
M
M
Montreal Neurological Institute, Que., Canada.
D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D004827:Epilepsy / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008954:Models, Biological; D010477:Perfusion; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D011963:Receptors, GABA-A; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline