Epileptiform activity induced by 4-aminopyridine in rat amygdala neurons: the involvement of N-methyl-D-aspartate receptors.
The involvement of the N-methyl-D-aspartate (NMDA) receptor in the epileptiform activity induced by 4-aminopyridine (4-AP) was studied in rat amygdala slices using intracellular recording techniques. Stimulation of the ventral endopyriform nucleus evoked an excitatory postsynaptic potential (EPSP). After exposure to 4-AP (200 microM) the amygdala slices usually exhibited spontaneous and evoked epileptiform activity. The epileptiform events had an average duration of 522 +/- 78 ms with a frequency of 0.5-8.5 bursts/min. Superfusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a selective non-NMDA receptor antagonist, practically abolished the epileptiform bursting. However, there remained a residual depolarizing component in 13 out of 18 neurons. This CNQX-resistant component was markedly enhanced both in amplitude and duration when extracellular Mg2+ was removed and could be reversibly blocked by the specific NMDA receptor antagonist, DL-2-amino-5-phosphonovaleate (DL-APV). Compared with the CNQX-sensitive component, the APV-sensitive component had a much smaller amplitude shorter duration. These data suggest that the NMDA receptor is likely to play only a minor role, and activation of the NMDA receptor may contribute to but is not required, for the generation of these bursts.
Gean
P W
PW
Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan City, Taiwan, Republic of China.
Chou
S M
SM
Chang
F C
FC
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology*; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000679:Amygdala / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D000818:Animals; D002118:Calcium / Q000502:physiology; D004558:Electric Stimulation; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D015761:4-Aminopyridine; D002118:Calcium