Valproate modifies spontaneous excitation and inhibition at cortical synapses in vitro

Mark O. Cunningham, Gavin L. Woodhall, Roland S.G. Jones*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

The anticonvulsant, valproic acid (VPA), has a very wide spectrum of clinical activity and has conventionally been considered to act by enhancing inhibitory GABAergic activity, either by increasing GABA levels and its subsequent release or by enhancing postsynaptic GABA responses. However, the pharmacology of VPA is complex and other mechanisms may well contribute. In the present study, we examined the effect of the drug on the release of GABA and glutamate at synapses in the rat entorhinal cortex, using the whole-cell patch clamp technique to record spontaneous excitatory (sEPSCs) and inhibitory postsynaptic currents (sIPSCs). VPA reduced the frequency but not the amplitude of both spontaneous sEPSCs and sIPSCs, with a more pronounced effect on the former. However, VPA had no effect on miniature, monoquantal events recorded in the presence of TTX, suggesting that the reduction in release occurred via blockade of Na+-channels in the presynaptic neurones. In addition, VPA also prolonged the decay time of sIPSCs, and this effect was occluded by a benzodiazepine agonist, zolpidem. These data suggest that in addition to presynaptic effects on release, VPA can potentiate postsynaptic responses, possibly by interaction with the benzodiazepine regulatory site of the GABA A receptor.

Original languageEnglish
Pages (from-to)907-917
Number of pages11
JournalNeuropharmacology
Volume45
Issue number7
DOIs
Publication statusPublished - 1 Dec 2003

Fingerprint

Valproic Acid
Synapses
Inhibitory Postsynaptic Potentials
gamma-Aminobutyric Acid
Benzodiazepines
Entorhinal Cortex
Excitatory Postsynaptic Potentials
Patch-Clamp Techniques
GABA-A Receptors
Anticonvulsants
In Vitro Techniques
Glutamic Acid
Pharmacology
Neurons

Keywords

  • Entorhinal cortex
  • GABA release
  • Glutamate release
  • Valproate

Cite this

Cunningham, Mark O. ; Woodhall, Gavin L. ; Jones, Roland S.G. / Valproate modifies spontaneous excitation and inhibition at cortical synapses in vitro. In: Neuropharmacology. 2003 ; Vol. 45, No. 7. pp. 907-917.
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Valproate modifies spontaneous excitation and inhibition at cortical synapses in vitro. / Cunningham, Mark O.; Woodhall, Gavin L.; Jones, Roland S.G.

In: Neuropharmacology, Vol. 45, No. 7, 01.12.2003, p. 907-917.

Research output: Contribution to journalArticle

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