Release of GABA from rat hippocampal slices: involvement of quisqualate/N-methyl-D-aspartate-gated ionophores and extracellular magnesium.

Effects of glutamate agonists and their selective antagonists on the Ca(2+)-dependent release of [3H]GABA from rat hippocampal slices were studied in a superfusion system. The release was enhanced by glutamate, kainate, quisqualate, N-methyl-D-aspartate and glycine in a concentration-dependent manner. In general, (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohept-5,10-imine hydrogen maleate (MK-801) strongly antagonized the effects of all agonists tested in low-Mg2+ (0.1 mM) media. 6-Cyano-7-nitroquinoxaline-2,3-dione did not inhibit the effects of N-methyl-D-aspartate, quisqualate, glycine or N-methyl-D-aspartate together with glycine in 0.1 mM Mg2+ media. Extracellular Mg2+ failed to block the release elicited by the agonists alone. However, the action of N-methyl-D-aspartate was potentiated by glycine only in low-Mg2+ media. We suggest that under the present experimental conditions the activation of N-methyl-D-aspartate/low-affinity quisqualate receptors located presynaptically on excitatory fibre terminals and/or postsynaptically on GABAergic interneurons is essential in hippocampal GABA release. A functional interaction is proposed between glycine and extracellular Mg2+ in the modulation of the quisqualate N-methyl-D-aspartate-gated ionophores involved in this process.