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 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.

Inhibition of GABA release from slices prepared from several brain regions of rats at various times following a convulsion

“…They concluded that newly synthesized GABA is located in a pool different from that of [3H]-GABA taken up into the preparation and is not under the influence of GABA-transaminase. This conclusion is further corroborated by the work of Szerb et al (1981) who demonstrated that inclusion of gabaculline in a superfusion system containing rat cortical slices augmented the depolarization-induced release of [3HJ-GABA but not that of endogenous GABA.…”

“…endogenous GABA release using tissue slices in a superfusion model (Szerb et al, 1981). Basal tissue levels of GABA measured from the slices after incubation were higher than values obtained from microwave irradiation and the post-mortem rise in GABA levels is the probable explanation for the absence of any difference in basal GABA content between controls and ECS animals.…”

Endogenous GABA release is reduced in the striatum of cocaine-sensitized rats

“…Thus, endogenously and exogenously derived GABA release appear to be differently affected by cocaine sensitization. This is not surprising, however, because of possible differences in endogenous and exogenous GABA incorporation into intraterminal pools and subsequent differences in release in response to various stimuli (Abe and Matsuda, 1983;Lidén et al, 1987;Pin and Bockaert, 1989;Ryan and Toskoski, 1975;Sellström and Hamberger, 1977;Szerb, 1983;Szerb et al, 1981). Neuronal GABA exists in several intraterminal pools (see Fig, 4A): newly synthesized pools (S) and metabolic pools (M) filled via reuptake pumps.…”

“…Neuronal GABA exists in several intraterminal pools (see Fig, 4A): newly synthesized pools (S) and metabolic pools (M) filled via reuptake pumps. In these experiments, the released endogenous GABA could originate from both the newly synthesized pools and the metabolic pools (Abe and Matsuda, 1983;Ryan and Toskoski, 1975;Szerb, 1983;Szerb et al, 1981). Depletion of either of these pools could contribute to the decrease in endogenous GABA release seen in cocainesensitized rats (Fig.…”

“…4B). On the other hand, the source of radiolabeled or exogenous GABA release is solely the metabolic pools filled through reuptake (Abe and Matsuda, 1983;Szerb, 1983;Szerb et al, 1981). If cocaine sensitization depletes this pool, then incubation with [ 3 H]GABA might be expected to result in greater filling of these pools compared to naive rats (Fig.…”