4-aminopyridine-induced epileptiform activity and a GABA-mediated long-lasting depolarization in the rat hippocampus.
Two types of spontaneous filed potentials were recorded in rat hippocampal slices after addition of 4-aminopyridine (4-AP; 50 microM). One consisted of brief, epileptiform discharges that occurred at 0.6 +/- 0.2 sec-1 in the CA3 and CA1 areas. The other type occurred less frequently (0.036 +/- 0.013 sec-1) and was recorded in CA1, CA3, and dentate areas. It corresponded in all regions to an intracellular long-lasting depolarization (LLD; duration, 300-1200 msec; peak amplitude, 2-15 mV) that was abolished by bicuculline methiodide; therefore, it was mediated by GABAA receptors. Sectioning experiments and the occurrence of propagation failures indicated that LLDs could be initiated by any area of the slice. Furthermore, the propagation of LLDs did not follow any consistent or predictable pattern along known anatomical hippocampal pathways. Finally, neither the occurrence nor the propagation of LLDs was affected when excitatory synaptic transmission was blocked by NMDA and non-NMDA receptor antagonists. In the presence of antagonists of glutamatergic receptors, LLDs disappeared after the omission of Ca2+ or the addition of Cd2+ to the perfusing solution, suggesting that synaptic transmission was required for their generation. These data indicate that 4-AP discloses both interictal epileptiform discharges and LLDs in the rat hippocampus. The first type of activity is presumably related to certain properties of CA3 pyramidal neurons and the neuronal circuit, whereas LLDs originate from the spontaneous, periodic activity of GABAergic interneurons located in any area of the hippocampus, and can propagate to the other areas by the use of nonsynaptic mechanisms. We propose that 4-AP reveals a novel type of interaction among GABAergic interneurons that is based on the accumulation and the dispersion of K+.
Perreault
P
P
Montreal Neurological Institute, Québec, Canada.
Avoli
M
M
D015761:4-Aminopyridine / Q000494:pharmacology* / Q000633:toxicity; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology; D002529:Cerebellar Nuclei / Q000187:drug effects / Q000502:physiology; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter; D005680:gamma-Aminobutyric Acid; D015761:4-Aminopyridine; D002118:Calcium