Chapter

Chloride Homeostasis and GABA Signaling in Temporal Lobe Epilepsy

Richard Miles, Peter Blaesse, Gilles Huberfeld, Lucia Wittner and Kai Kaila

in Jasper's Basic Mechanisms of the Epilepsies

Fourth edition

Published on behalf of ©Jeffrey L. Noebels, Massimo Avoli, Michael A. Rogawski, Richard W. Olsen, and Antonio V. Delgado-Escueta

Published in print July 2012 | ISBN: 9780199746545
Published online April 2013 | e-ISBN: 9780199322817 | DOI: http://dx.doi.org/10.1093/med/9780199746545.003.0045

Series: Contemporary Neurology Series

Chloride Homeostasis and GABA Signaling in Temporal Lobe Epilepsy

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Defects in GABAergic signaling have often been linked to the epilepsies. Suppressing fast inhibition mediated by gamma-aminobutyric acid A (GABAA) receptors initiates interictal-like activities in healthy brain tissue,1,2 and specific subgroups of interneurons seem to be especially sensitive to the neuronal death associated with temporal lobe epileptic syndromes.3–5 However, defects in the neuronal homeostasis of chloride have only recently been linked to epileptiform activities. Intraneuronal levels of chloride control GABAergic signaling postsynaptically.6 So, changes in chloride homeostasis can affect the strength and even the sign of GABAergic signals. We will describe work on tissue from patients with pharmacoresistant epilepsies of the temporal lobe that provided the first insight that chloride homeostasis might be altered in the epilepsies.7,8 We will examine molecules that control chloride homeostasis, evidence that they are modulated by pathological stressors including denervation, anoxia and the sclerotic cell death associated with some focal epilepsies. We ask whether changes in chloride homeostasis contribute to ictal events, arguing that potassium efflux mediated by K-Cl cotransporters may contribute to prolonged ictal excitation. Finally, we examine how differences in chloride regulation may contribute to neonatal epilepsies and ask whether molecules targeting chloride homeostasis might be effective anti-epileptic drugs.

Chapter.  6614 words.  Illustrated.

Subjects: Neurology

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