Synaptosomal glutamate and GABA transport in patients with temporal lobe epilepsy
Article first published online: 3 MAY 2004
Copyright © 2004 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 76, Issue 6, pages 881–890, 15 June 2004
How to Cite
Hoogland, G., Spierenburg, H.A., van Veelen, C.W.M., van Rijen, P.C., van Huffelen, A.C. and de Graan, P.N.E. (2004), Synaptosomal glutamate and GABA transport in patients with temporal lobe epilepsy. J. Neurosci. Res., 76: 881–890. doi: 10.1002/jnr.20128
- Issue published online: 19 MAY 2004
- Article first published online: 3 MAY 2004
- Manuscript Revised: 13 FEB 2004
- Manuscript Accepted: 13 FEB 2004
- Manuscript Received: 8 DEC 2003
- Epilepsy Fund of The Netherlands. Grant Number: A91
- glutamate transporters;
- GABA transporters;
High-affinity glutamate and GABA transporters found in the plasma membrane of neurons and glial cells terminate neurotransmission by rapidly removing extracellular transmitter. Impairment of transporter function has been implicated in the pathophysiologic mechanisms underlying epileptogenesis. We characterized glutamate and γ-aminobutyric acid (GABA) transport in synaptosomes, isolated from neocortical and hippocampal biopsies of patients with temporal lobe epilepsy (TLE). We analyzed K+-evoked release in the presence and absence of Ca2+ to determine vesicular and transporter-mediated release, respectively. We also analyzed 3H-glutamate and 3H-GABA uptake, the effect of glutamate uptake inhibitors L-trans-pyrrolidine-2,4-dicarboxylic acid (tPDC) and DL-threo-β-benzyloxyaspartate (TBOA), and GABA uptake inhibitor N-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylic acid (SK&F 89976-A). Neocortical synaptosomes from TLE patients did not show vesicular glutamate release, strongly reduced transporter-mediated release, and an increased basal release compared to that in rat synaptosomes. Furthermore, basal release was less sensitive to tPDC, and 3H-glutamate uptake was reduced compared to that in rat synaptosomes. Vesicular GABA release from neocortical synaptosomes of TLE patients was reduced compared to that in rat synaptosomes, whereas transporter-mediated release was hardly affected. Furthermore, basal GABA release was more than doubled, but neither basal nor stimulated release were increased by SK&F 89976-A, which did significantly increase both types of GABA release in rat synaptosomes. Finally, 3H-GABA uptake by synaptosomes from TLE patients was reduced significantly in hippocampus (0.19 ± 0.04%), compared to that in neocortex (0.32 ± 0.04%). Control experiments with human peritumoral cortical tissue suggest that impaired uptake of glutamate, but not of GABA, was caused in part by the hypoxic state of the biopsy. Our findings provide evidence for impaired function of glutamate and GABA transporters in human TLE. © 2004 Wiley-Liss, Inc.