Faculty Collaboration Database

Anticonvulsant action of GABA in the high potassium-low magnesium model of ictogenesis in the neonatal rat hippocampus in vivo and in vitro. J Neurophysiol 2005 Oct;94(4):2987-92

Date

07/08/2005

Pubmed ID

16000527

DOI

10.1152/jn.00138.2005

Scopus ID

2-s2.0-24944535227 (requires institutional sign-in at Scopus site)   32 Citations

Abstract

Previous developmental studies in vitro suggested that the inhibitory neurotransmitter GABA exerts depolarizing and excitatory actions on the immature neurons and that depolarizing GABA is causally linked to ictal activity during the first weeks of postnatal life. However, remarkably little is known on the role of GABA in the generation of neonatal seizures in vivo. Here, using extracellular recordings from CA3 hippocampus, we studied the effects of GABA(A)-acting drugs on electrographic seizures induced by local intrahippocampal injection of the epileptogenic agents (high K(+)/low Mg(2+)) in the nonanesthetized rats in vivo and in the hippocampal slices in vitro during the second postnatal week (postnatal days P8-12). We found that in vivo, the induction of ictal-like events was facilitated by co-infusion of high-K(+)/low Mg(2+) together with the GABA(A) antagonist bicuculline or gabazine. Moreover, the infusion of bicuculline alone caused ictal-like activity in approximately 30% of cases. Co-infusion of the GABA(A) receptor agonist isoguvacine or the GABA(A)-positive allosteric modulator diazepam completely prevented high-K(+)/low Mg(2+)-induced seizures. In in vitro studies using hippocampal slices, we also found that high-K(+)/low Mg(2+) produced ictal activity that was exacerbated by bicuculline and gabazine and reduced by isoguvacine. Thus in the model of high-K(+)/low Mg(2+)-induced seizures both in in vivo and in vitro conditions, GABA, acting via GABA(A) receptors, has an anticonvulsant effect during the critical developmental period of enhanced excitability.

Author List

Isaev D, Isaeva E, Khazipov R, Holmes GL

Author

Olena Isaeva PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

2-Amino-5-phosphonovalerate
6-Cyano-7-nitroquinoxaline-2,3-dione
Animals
Animals, Newborn
Bicuculline
Disease Models, Animal
Drug Interactions
Excitatory Amino Acid Antagonists
GABA Agonists
GABA Antagonists
Hippocampus
In Vitro Techniques
Isonicotinic Acids
Lipoproteins
Magnesium
Membrane Potentials
Neurons
Patch-Clamp Techniques
Potassium
Pyridazines
Rats
Seizures
gamma-Aminobutyric Acid