The epileptiform activity induced by 4-aminopyridine in rat amygdala slices: antagonism by non-N-methyl-D-aspartate receptor antagonists.
The effects of excitatory amino acid receptor antagonists kynuretic acid and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on epileptiform activity induced by 4-aminopyridine (4-AP) were studied in rat amygdala slices using intracellular recording techniques. Five to 10 min after switching to 4-AP-containing solution, spontaneous epileptiform bursts were observed in 35 out of 45 slices studied. The spontaneous epileptiform events consisted of an initial burst followed by a number of afterdischarges. Superfusion with kynuretic acid, a broad-spectrum excitatory amino acid receptor antagonist, reversibly reduced the duration of the spontaneous bursting discharges in a dose-dependent manner. The frequency of spontaneous bursting was also decreased. The IC50, estimated from the graph of the concentration-response relationship, was approximately 130 microM. In addition, CNQX which is a specific non-N-methyl-D-aspartate (NMDA) receptor antagonist blocked the spontaneous and evoked epileptiform bursting. In 11 out of 15 neurons tested, there was a residual depolarizing component remained. This depolarizing component was reversibly blocked by specific NMDA receptor antagonist, D,L-2-amino-5-phosphonovaleate (D,L-APV). Relative to the CNQX-sensitive component, the D,L-APV-sensitive component is much smaller in amplitude and shorter in duration indicating that NMDA receptor plays only a minor role in this process. These data suggest that the generation or propagation of spontaneous epileptiform events induced by 4-AP in the neurons of basolateral amygdala is mediated by excitatory amino acids and that activation of non-NMDA receptors is of primary importance.
Gean
P W
PW
Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan.
D015761:4-Aminopyridine / Q000494:pharmacology*; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D004594:Electrophysiology; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology
D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015761:4-Aminopyridine