Development of changes in endogenous GABA release during kindling epileptogenesis in rat hippocampus.

The calcium-dependent gamma-aminobutyric acid (GABA) and glutamate release from rat hippocampal CA1 slices, evoked by a 1-min depolarization with 50 mM K+, was investigated in different stages of kindling epileptogenesis. Kindling was induced by tetanic stimulation of the Schaffer collateral/commissural pathway. In agreement with our previous results, we found a significantly increased calcium-dependent GABA release compared to that of implanted controls, in a group of fully kindled animals 1 day after the last seizure and also 25-36 days after the last seizure. In addition, we found that the increase in GABA release was associated with late phases of kindling epileptogenesis since no significant alterations were found in partly kindled animals that had received only 6 kindling stimulations while a significant increase was apparent in animals that had received 14 tetanic stimuli. When the release protocol was carried out in the presence of SK&F 89776-A, a blocker of the GABA uptake carrier, an additional amount of GABA was found after depolarization. This additional amount of GABA, reflecting the amount of GABA taken up under conditions without blocker, was in kindled animals not different from controls which demonstrates that a reduced GABA uptake does not account for the observed enhanced release in kindled animals. The calcium-dependent release of glutamate evoked by 1 min of high potassium depolarization was not significantly changed in the kindled groups. Only after prolonged depolarization during 4 subsequent minutes a significant increase in animals of the fully kindled group and at long-term after kindling was observed. The threshold K+ concentration for eliciting a calcium-dependent release of GABA and glutamate, was not changed in the kindled animals.(ABSTRACT TRUNCATED AT 250 WORDS)