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Shunting and hyperpolarizing GABAergic inhibition in the high‐potassium model of ictogenesis in the developing rat hippocampus
Author(s) -
Isaev Dmytro,
Isaeva Elena,
Khazipov Rustem,
Holmes Gregory L.
Publication year - 2007
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.20259
Subject(s) - gabaa receptor , gabaergic , chemistry , neuroscience , depolarization , hippocampus , bicuculline , gaba receptor , hippocampal formation , nipecotic acid , medicine , endocrinology , receptor , biology , neurotransmitter , biochemistry
Ontogenesis of GABAergic signaling may play an important role in developmental changes in seizure susceptibility in the high‐potassium model of ictogenesis in vitro. The age‐dependent effects of [K + ] o on the reversal potential of the GABA(A)‐mediated responses and membrane potential in hippocampal slices in vitro were compared with the effect of GABA(A)‐receptors antagonists and GABA(A) modulators on high‐potassium induced seizures in the CA3 pyramidal layer of rat hippocampus in vivo. GABA(A) responses were depolarizing at P8–12 and hyperpolarizing at P17–21. In P8–12 rats, GABA(A) responses switch their polarity from depolarizing to hyperpolarizing upon elevation of extracellular potassium. At ∼10 mM [K + ] o , activation of GABA(A) receptors produced an isoelectric, purely shunting response characterized by no changes in the membrane potential but an increase in the membrane conductance. In P17–21 rats, the hyperpolarizing GABA(A) driving force progressively increased with elevation of [K + ] o . In P8–12 rats in vivo, GABA(A)‐receptor antagonists did not affect the occurrence of ictal discharges induced by intrahippocampal injection of 10 mM [K + ] o , but significantly increased seizure duration. Diazepam and isoguvacine completely prevented seizures induced by 10 mM [K + ] o . In P17–21 rats, GABA(A)‐receptor antagonists strongly increased the occurrence of ictal activity induced both by 10 mM [K + ] o . Taken together, these results suggest that anticonvulsive effects of GABA are because of the combination of shunting and hyperpolarizing actions of GABA. Although shunting GABA is already efficient in the young age group, a developmental increase in the hyperpolarizing GABA(A) driving force likely contributes to the increase in the GABAergic control of seizures upon maturation. © 2007 Wiley‐Liss, Inc.