Zinc-induced collapse of augmented inhibition by GABA in a temporal lobe epilepsy model.
In the kindling model of temporal lobe epilepsy, several physiological indicators of inhibition by gamma-aminobutyric acid (GABA) in the hippocampal dentate gyrus are consistent with an augmented, rather than a diminished, inhibition. In brain slices obtained from epileptic (kindled) rats, the excitatory drive onto inhibitory interneurons was increased and was paralleled by a reduction in the presynaptic autoinhibition of GABA release. This augmented inhibition was sensitive to zinc most likely after a molecular reorganization of GABAA receptor subunits. Consequently, during seizures, inhibition by GABA may be diminished by the zinc released from aberrantly sprouted mossy fiber terminals of granule cells, which are found in many experimental models of epilepsy and in human temporal lobe epilepsy.
Buhl
E H
EH
Anatomical Neuropharmacology Unit, Oxford University, UK.
Otis
T S
TS
Mody
I
I
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002712:Chlorides / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology*; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006801:Humans; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*; D017967:Zinc Compounds / Q000494:pharmacology; D000077334:Zolpidem; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002712:Chlorides; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D011725:Pyridines; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D017967:Zinc Compounds; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D000077334:Zolpidem; C016837:zinc chloride; D015032:Zinc