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Hippocampal GABA transporter function in temporal-lobe epilepsy

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Abstract

ELECTROPHYSIOLOGICAL studies of human temporal-lobe epilepsy suggest that a loss of hippocampal GABA-mediated inhibition may underlie the neuronal hyperexcitability1–3. However, GABA (γ-aminobutyric acid)-containing cells are preserved4and GABA receptors are maintained in the surviving hippocampal neurons5. Diminished GABA release may therefore mediate the loss of inhibition. Here we show that, in the human brain, potassium-stimulated release of GABA was increased, and glutamate-induced, calcium-independent release of GABA was markedly decreased, in epileptogenic hippocampi, in contrast with contra-lateral, non-epileptogenic hippocampi. The glutamate-induced GABA release in vivo was transporter-mediated in rats. Furthermore, in amygdala-kindled rats, a model for human epilepsy, a decrease in glutamate-induced GABA release was associated with a 48% decrease in the number of GABA transporters. These data suggest that temporal-lobe epilepsy is characterized in part by a loss of glutamate-stimulated GABA release that is secondary to a reduction in the number of GABA transporters.

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Authors and Affiliations

  1. Molecular Pharmacology and Neurogenetics Laboratory, Sections of Neurosurgery and Endocrinology, Departments of Surgery and Internal Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut, 06510, USA

    Matthew J. During, Kathryn M Ryder & Dennis D. Spencer

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  1. Matthew J. During
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  2. Kathryn M Ryder
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  3. Dennis D. Spencer
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During, M., Ryder, K. & Spencer, D. Hippocampal GABA transporter function in temporal-lobe epilepsy. Nature 376, 174–177 (1995). https://doi.org/10.1038/376174a0

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