Hippocampal GABA transporter function in temporal-lobe epilepsy.
Electrophysiological studies of human temporal-lobe epilepsy suggest that a loss of hippocampal GABA-mediated inhibition may underlie the neuronal hyperexcitability. However, GABA (gamma-aminobutyric acid)-containing cells are preserved and GABA receptors are maintained in the surviving hippocampal neurons. 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 contralateral, 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.
During
M J
MJ
Department of Surgery, Yale University School of Medicine, Connecticut 06510, USA.
Ryder
K M
KM
Spencer
D D
DD
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism*; D050485:GABA Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D017551:Microdialysis; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D027361:Organic Anion Transporters; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D011188:Potassium