Differences in cortical versus subcortical GABAergic signaling: a candidate mechanism of electroclinical uncoupling of neonatal seizures.

Full Abstract

Electroclinical uncoupling of neonatal seizures refers to electrographic seizure activity that is not clinically manifest. Uncoupling increases after treatment with Phenobarbital, which enhances the GABA(A) receptor (GABA(A)R) conductance. The effects of GABA(A)R activation depend on the intracellular Cl(-) concentration ([Cl(-)](i)) that is determined by the inward Cl(-) transporter NKCC1 and the outward Cl(-) transporter KCC2. Differential maturation of Cl(-) transport observed in cortical versus subcortical regions should alter the efficacy of GABA-mediated inhibition. In perinatal rat pups, most thalamic neurons maintained low [Cl(-)](i) and were inhibited by GABA. Phenobarbital suppressed thalamic seizure activity. Most neocortical neurons maintained higher [Cl(-)](i), and were excited by GABA(A)R activation. Phenobarbital had insignificant anticonvulsant responses in the neocortex until NKCC1 was blocked. Regional differences in the ontogeny of Cl(-) transport may thus explain why seizure activity in the cortex is not suppressed by anticonvulsants that block the transmission of seizure activity through subcortical networks.

Author information

Author/s: Glykys, Joseph (J); Dzhala, Volodymyr I (VI); Kuchibhotla, Kishore V (KV); Feng, Guoping (G); Kuner, Thomas (T); Augustine, George (G); Bacskai, Brian J (BJ); Staley, Kevin J (KJ);

Affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA.

Grants: EB000768 (Agency:NIBIB NIH HHS) ; NS040109 (Agency:NINDS NIH HHS) ; NS580752 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Neuron (Neuron), published in United States. (Language: eng)

Reference: 2009-Sep; vol 63 (issue 5) : pp 657-72

Dates: Created 2009/09/16; Completed 2009/10/13;

PMID: 19755108, status: MEDLINE (last retrieval date: 10/13/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Amygdala - growth & development; physiopathology
Animals
Animals, Newborn
Anticonvulsants - pharmacology
Bumetanide - pharmacology
Chlorides - metabolism
Female
Male
Neocortex - drug effects; growth & development; physiopathology
Neurons - physiology
Phenobarbital - pharmacology

Associated Chemicals: Anticonvulsants (0) ; Chlorides (0) ; Receptors, GABA-A (0) ; Sodium Potassium Chloride Symporter Inhibitors (0) ; Sodium-Potassium-Chloride Symporters (0) ; sodium-potassium-chloride cotransporter 1 protein (0) ; Bumetanide (28395-03-1) ; Phenobarbital (50-06-6) ; gamma-Aminobutyric Acid (56-12-2)

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