Ethosuximide modifies network excitability in the rat entorhinal cortex via an increase in GABA release

Greenhill, Stuart D., Massey, Peter, Morgan, Nicola, Woodhall, Gavin and Jones, Roland S.G. (2012). Ethosuximide modifies network excitability in the rat entorhinal cortex via an increase in GABA release. Neuropharmacology, 62 (2), pp. 807-814.

Abstract

Ethosuximide is the drug of choice for treating generalized absence seizures, but its mechanism of action is still a matter of debate. It has long been thought to act by disrupting a thalamic focus via blockade of T-type channels and, thus, generation of spike-wave activity in thalamocortical pathways. However, there is now good evidence that generalized absence seizures may be initiated at a cortical focus and that ethosuximide may target this focus. In the present study we have looked at the effect ethosuximide on glutamate and GABA release at synapses in the rat entorhinal cortex in vitro, using two experimental approaches. Whole-cell patch-clamp studies revealed an increase in spontaneous GABA release by ethosuximide concurrent with no change in glutamate release. This was reflected in studies that estimated global background inhibition and excitation from intracellularly recorded membrane potential fluctuations, where there was a substantial rise in the ratio of network inhibition to excitation, and a concurrent decrease in excitability of neurones embedded in this network. These studies suggest that, in addition to well-characterised effects on ion channels, ethosuximide may directly elevate synaptic inhibition in the cortex and that this could contribute to its anti-absence effects. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

Publication DOI: https://doi.org/10.1016/j.neuropharm.2011.09.006
Divisions: Life & Health Sciences
Life & Health Sciences > Pharmacy
?? NABC ??
Additional Information: © 2011, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Uncontrolled Keywords: entorhinal cortex,anticonvulsants,presynaptic terminals,ethosuximide,glutamate release,GABA release,excitability,Cellular and Molecular Neuroscience,Pharmacology
Full Text Link:
Related URLs: http://www.scopus.com/inward/record.url?scp=84855916993&partnerID=8YFLogxK (Scopus URL)
Published Date: 2012-02
Authors: Greenhill, Stuart D. ( 0000-0002-5038-5258)
Massey, Peter
Morgan, Nicola
Woodhall, Gavin ( 0000-0003-1281-9008)
Jones, Roland S.G.

Download

[img]

Version: Accepted Version

| Preview

Export / Share Citation


Statistics

Additional statistics for this record