Differential Calcium Dependence of γ-Aminobutyric Acid and Acetylcholine Release in Mouse Brain Synaptosomes

The dependence of gamma-aminobutyric acid (GABA) and acetylcholine (ACh) release on Ca2+ was comparatively studied in synaptosomes from mouse brain, by correlating the influx of 45Ca2+ with the release of the transmitters. It was observed that exposure of synaptosomes to a Na+-free medium notably increases Ca2+ entry, and this condition was used, in addition to K+ depolarization and the Ca2+ ionophore A23187, to stimulate the influx of Ca2+ and the release of labeled GABA and ACh. The effect of ruthenium red (RuR) on these parameters was also investigated. Of the three experimental conditions used, the absence of Na+ in the medium proved to be the most efficient in increasing Ca2+ entry. RuR inhibited by 60-70% the influx of Ca2+ stimulated by K+ depolarization but did not affect its basal influx or its influx stimulated by the absence of Na+ or by A23187. The release of ACh was stimulated by K+ depolarization, absence of Na+ in the medium, and A23187 in a strictly Ca2+-dependent manner, whereas the release of GABA was only partially dependent on the presence of Ca2+ in the medium. The extent of stimulation of ACh release was related to the extent of Ca2+ entry, whereas no such correlation was observed for GABA. In the presence of Na+, RuR did not affect the release of the transmitters induced by A23187. In the absence of Na+, paradoxically RuR notably enhanced the release of both ACh and GABA induced by A23187, in a Ca2+-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)