Turnover and release of GABA in rat cortical slices: effect of a GABA-T inhibitor, gabaculine

• Published in: Neurochemical research Vol. 7; no. 2; p. 191
• Main Author: Szerb, J C
• Format: Journal Article
• Language: English
• Published: United States 01.02.1982
• Subjects: 4-Aminobutyrate Transaminase - antagonists & inhibitors; 4-Aminobutyrate Transaminase - metabolism; Animals; Calcium - pharmacology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Culture Techniques; Cyclohexanecarboxylic Acids - pharmacology; gamma-Aminobutyric Acid - metabolism; Neuroglia - metabolism; Potassium - pharmacology; Rats; Rats, Inbred Strains; Tritium
• ISSN: 0364-3190
• DOI: 10.1007/BF00965057

The turnover and release of endogenous and labeled GABA were followed in rat cortical slices after incubation with [3H]GABA. High performance liquid chromatography was used to measure endogenous GABA and to separate [3H]GABA from its metabolites. During superfusion with 3 mM K+ the slices rapidly lost their [3H]GABA content while maintaining constant GABA levels. Exposure to 50 mM K+ for 25 min caused an initial rapid rise in the release of both endogenous and [3H]GABA followed by a more rapid decline in the release of the latter. The specific activity of released GABA was two to four times higher than that in the slices. Depolarization lead to a net synthesis of GABA. The GABA -T inhibitor, gabaculine, (5 micrometers) in vitro arrested the metabolism of [3H]GABA and rapidly doubled the GABA content but did not significantly increase the high K+ evoked release of endogenous GABA. In vivo pretreatment with 0.5 mM/kg gabaculine quadrupled GABA content and increased both the spontaneous and evoked release of endogenous GABA but while its Ca2+ -dependent release increased by 50%, the Ca2+ -independent release was enhanced sevenfold. This large Ca2+ -independent release of GABA is likely to have different functional significance from the normal Ca2+ -dependent release.