Selective antagonism of GluR5 kainate-receptor-mediated synaptic currents by topiramate in rat basolateral amygdala neurons

Divina S. Gryder, Michael A Rogawski

Research output: Contribution to journalArticle

175 Scopus citations

Abstract

Topiramate is a widely used antiepileptic agent whose mechanism of action is poorly understood. The drug has been reported to interact with various ion channel types, including AMPA/kainate receptors. In whole-cell voltage-clamp recordings from principal neurons of the rat basolateral amygdala, topiramate at low concentrations (IC50, ∼0.5 μM) selectively inhibited pharmacologically isolated excitatory synaptic currents mediated by kainate receptors containing the GluR5 subunit. Topiramate also partially depressed predominantly AMPA-receptor-mediated EPSCs, but with lower efficacy. Topiramate did not alter the degree of facilitation in paired-pulse experiments, and it reduced the amplitude of miniature EPSCs without affecting their frequency, demonstrating that the block of synaptic responses occurs postsynaptically. Inhibition of GluR5 kainate receptors could represent a key mechanism underlying the anticonvulsant activity of topiramate. Moreover, these results support the concept that GluR5 kainate receptors represent a novel target for antiepileptic drug development.

Original languageEnglish (US)
Pages (from-to)7069-7074
Number of pages6
JournalJournal of Neuroscience
Volume23
Issue number18
StatePublished - Aug 6 2003
Externally publishedYes

Keywords

  • AMPA receptor
  • Amygdala
  • Kainate receptor
  • Patch-damp recording
  • Synaptic current
  • Topiramate

ASJC Scopus subject areas

  • Neuroscience(all)

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