Compartments of labeled and endogenous gamma-aminobutyric acid giving rise to release evoked by potassium or veratridine in rat cortical slices.

To establish compartments involved in depolarization-induced release of gamma-aminobutyric acid (GABA) in rat brain slices, the amount of exogenous labeled and endogenous GABA released and retained was followed during 48 min exposure to 50 mM-K+ or to 50 microM-veratridine. Endogenous GABA was measured with high performance liquid chromatography. The presence of 10 microM-aminooxyacetic acid throughout prevented both the metabolism of GABA and the formation of endogenous GABA due to depolarization. During superfusion with 50 mM-K+ and 2.6 nM-Ca2+ the efflux of labeled and endogenous GABA after an initial large increase declined to 10% of the highest value with constant and identical rates. Kinetic analysis of efflux showed that 10% of endogenous and 25% of labeled GABA present is available for release by high K+ and Ca2+. In the absence of Ca2+, release by high K+ of both labeled and endogenous GABA was nearly suppressed. Veratridine, unlike high K+, caused an efflux which declined with an initial fast and late very slow phase. The slow efflux by veratridine was doubled in the absence of Ca2+. Exposure to veratridine in the absence of Ca2+ during 120 min released nearly 70% of labeled and endogenous GABA present. Results suggest that only about 0.25 mumol . g-1 endogenous GABA is the source of physiological Ca2+-dependent release, while much of the remaining GABA present is released only under unphysiological conditions.