Effects of 3-aminoglutarate, a "silent" false transmitter for glutamate neurons, on synaptic transmission and epileptiform activity

Zheng Wu, Alan C. Foster, Ursula Staubli, Xia Wu, Chicheng Sun, Xin Tang, Yong Xin Li, Gong Chen

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Pharmacological tools that interact with the mechanisms that regulate vesicular filling and release of the neurotransmitter l-glutamate would be of enormous value. In this study, we provide physiological evidence that the glutamate analog, 3-aminoglutarate (3-AG), acts as a false transmitter to reduce presynaptic glutamate release. 3-AG inhibits glutamate-mediated neurotransmission both in primary neuronal cultures and in brain slices with more intact neural circuits. When assayed with the low affinity glutamate receptor antagonist γ-DGG, we demonstrate that 3-AG significantly reduces the synaptic cleft glutamate concentration, suggesting that 3-AG may act as a false transmitter to compete with glutamate during vesicle filling. Furthermore, using three different epileptic models (Mg2+-free, 4-AP, and high K+), we demonstrate that 3-AG is capable of suppressing epileptiform activity both before and after its induction. Our studies, along with those of the companion paper by Foster et al. (2015) indicate that 3-AG is a "silent" false transmitter for glutamate neurons that is a useful pharmacological tool to probe the mechanisms governing vesicular storage and release of glutamate under both physiological and pathophysiological conditions. 3-AG may have potential therapeutic value in conditions where the glutamate neurotransmitter system is pathologically overactive.

Original languageEnglish (US)
Pages (from-to)95-103
Number of pages9
JournalNeuropharmacology
Volume97
DOIs
StatePublished - Jun 25 2015

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

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