Seizure-like activity in the disinhibited CA1 minislice of adult guinea-pigs.
Spontaneous activity was monitored during pharmacological blockade of GABA(A) receptor function in the CA1 minislice (CA3 was cut off). Synaptic inhibition was blocked by competitive GABA(A) antagonists bicuculline-methiodide (Bic) or GABAZINE (GBZ) and the chloride channel blocker picrotoxin (PTX). Extra- and intracellular recordings using sharp electrodes were carried out in stratum radiatum and pyramidale. At low antagonist concentrations (Bic, GBZ: 1-10 microM; PTX: < 100 microM), synchronized bursts (< 500 ms in duration, interictal activity) were seen as described previously. However, in the presence of high concentrations (Bic, GBZ: 50-100 microM; PTX: 100-200 microM), seizure-like, ictal events (duration 4-17 s) were observed in 67 of 88 slices. No other experimental measures to increase excitability were applied: cation concentrations ([Ca2+]o = 2 mM, [Mg2+]o = 1.7 mM, [K+]o = 3 mM) and recording temperature (30-32 degrees C) were standard and GABA(B)-mediated inhibition was intact. In whole-slice recordings prominent interictal activity, but fewer ictal events were observed. A reduced ictal activity was also observed when interictal-like responses were evoked by afferent stimulation. Ictal activity was reversibly blocked by antagonists of excitatory transmission, CNQX (40 microM) or D-AP5 (50 microM). Disinhibition-induced ictal development did not rely on group I mGluR activation as it was not prevented in the presence of group I mGluR antagonists (AIDA or 4CPG). (RS)-3,5-DHPG prevented the induction and reversed the tertiary component of the ictal event through a group I mGluR-independent mechanism.
Karnup
S
S
Department of Physiology and Pharmacology, Box 29, State University of New York, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
Stelzer
A
A
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000367:Age Factors; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology / Q000503:physiopathology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology; D009924:Organ Culture Techniques; D010852:Picrotoxin / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D012118:Resorcinols / Q000494:pharmacology
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001640:Bicuculline; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D005998:Glycine; D010852:Picrotoxin; D011724:Pyridazines; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D012118:Resorcinols; C104077:metabotropic glutamate receptor type 1; C017069:bicuculline methiodide; C079215:3,5-dihydroxyphenylglycine; C049853:gabazine