Zinc-induced collapse of augmented inhibition by GABA in a temporal lobe epilepsy model

In the kindling model of temporal robe 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 GABA(A) receptor subunits. Consequently, during seizures, inhibition by GABA may be diminished by the zinc released from aberrantly sprouted messy fiber terminals of granule cells, which are found in many experimental models of epilepsy and in human temporal robe epilepsy.