Shunting and hyperpolarizing GABAergic inhibition in the high-potassium model of ictogenesis in the developing rat hippocampus.

Shunting and hyperpolarizing GABAergic inhibition in the high-potassium model of ictogenesis in the developing rat hippocampus. Research Abstract Details 

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Shunting and hyperpolarizing GABAergic inhibition in the high-potassium model of ictogenesis in the developing rat hippocampus. Abstract Text:

Dmytro Isaev,Elena Isaeva,Rustem Khazipov,Gregory L Holmes,

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 approximately 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.

Shunting and hyperpolarizing GABAergic inhibition in the high-potassium model of ictogenesis in the developing rat hippocampus. Publishing Authors By Initials

D Isaev,E Isaeva,R Khazipov,GL Holmes,

For similar organic chemicals: carboxylic acids: acids, acyclic: butyric acids: aminobutyric acids: gamma-aminobutyric acid research abstracts see: organic chemicals: carboxylic acids: acids, acyclic: butyric acids: aminobutyric acids: gamma-aminobutyric acid research

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Shunting and hyperpolarizing GABAergic inhibition in the high-potassium model of ictogenesis in the developing rat hippocampus. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Hippocampus

VOLUME: 17

Page Numbers: 210-9

Journal Abbreviation:

ISSN: 1050-9631

DAY: 3

MONTH: 12

YEAR: 2007

Shunting and hyperpolarizing GABAergic inhibition in the high-potassium model of ictogenesis in the developing rat hippocampus. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9108167

Shunting and hyperpolarizing GABAergic inhibition in the high-potassium model of ictogenesis in the developing rat hippocampus. Keywords Mesh Terms:

KEYWORDS: gamma-Aminobutyric Acid

MESH TERMS: metabolism

Chemical & Substance for Abstract: Shunting and hyperpolarizing GABAergic inhibition in the high-potassium model of ictogenesis in the developing rat hippocampus. Information

Substance Name: Potassium

Registry Number: 7440-09-7

Grant and Affiliation Information for Shunting and hyperpolarizing GABAergic inhibition in the high-potassium model of ictogenesis in the developing rat hippocampus.

AFFILIATION: Section of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA. dmytro.s.isaev@dartmouth.edu

Country: United States

AGENCY: United States NINDS

GRANT: NS44296

ACRONYM: NS

MEDLINETA: Hippocampus

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