Compartments of Labeled and Endogenous γ‐Aminobutyric Acid Giving Rise to Release Evoked by Potassium or Veratridine in Rat Cortical Slices

Abstract

— To establish compartments involved in depolarization-induced release of γ-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 μm-veratridine. Endogenous GABA was measured with high performance liquid chromatography. The presence of 10 μm-aminooxyacetic acid throughout prevented both the metabolism of GABA and the formation of endogenous GABA due to depolarization. During super-fusion with 50 mm-K⁺ and 2.6 mm-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 μmol 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.