کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2493778 1115528 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Ethosuximide modifies network excitability in the rat entorhinal cortex via an increase in GABA release
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Ethosuximide modifies network excitability in the rat entorhinal cortex via an increase in GABA release
چکیده انگلیسی

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’.


► We investigate the effect of the ethosuximide, on cortical synaptic transmission.
► Spontaneous GABA release is increased but glutamate release is unaffected.
► Global inhibition is elevated resulting in an increase in inhibition:excitation ratio.
► Excitability of the network is decreased.
► Elevation of GABA release may dampen the cortical focus in absence seizures.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 62, Issue 2, February 2012, Pages 807–814
نویسندگان
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