Unaltered control of extracellular GABA-concentration through GAT-1 in the hippocampus of rats after pilocarpine-induced status epilepticus.
The uptake of the inhibitory transmitter GABA (gamma-aminobutyric acid) limits the efficacy of synaptic and tonic inhibition in brain tissue. It has been reported that GABA-uptake is down-regulated in temporal lobe epilepsy. This down-regulation may increase the inhibitory action of GABA but may also limit the anticonvulsant activity of GABA-uptake blockers. We have directly compared the function of GABA-uptake in hippocampal slices from normal and chronically epileptic rats. We raised the global extracellular concentration of GABA by bath-application of the agonist in the absence and presence of the GABA-uptake blocker tiagabine. GABA-induced currents were measured in dentate granule cells and CA1 pyramidal neurons in hippocampal slices. The potentiation of currents by tiagabine was taken as a measure for the efficacy of GABA-uptake in the hippocampal tissue. There was no difference between cells from control- or pilocarpine-treated animals in the response to GABA or in the conductance increase following application of tiagabine. Our data show that in the chronic phase of the pilocarpine-model GABA-uptake maintains its ability to control the extracellular background concentration of GABA.
Frahm
Christiane
C
Johannes-Müller-Institut für Physiologie der Charité, Tucholskystr. 2, 10117, Berlin, Germany.
Stief
Frank
F
Zuschratter
Werner
W
Draguhn
Andreas
A
D000818:Animals; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D018721:Muscarinic Agonists; D009557:Nipecotic Acids / Q000494:pharmacology; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced* / Q000503:physiopathology; D000078308:Tiagabine; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018755:GABA Agonists; D018721:Muscarinic Agonists; D009557:Nipecotic Acids; D010862:Pilocarpine; D005680:gamma-Aminobutyric Acid; D000078308:Tiagabine