ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: The effect of EGTA on the release of labeled γ-aminobutyric acid (GABA), glutamate, acetylcholine, and dopamine was studied in superfused synaptosomes from mouse brain. In the absence of both Ca2+ and Mg2+, EGTA and also EDTA at 50 μM or higher concentrations induced a 2.5-5-fold stimulation of [3H]GABA release, similar to that produced by potassium depolarization, whereas only a slight effect, or no effect at all, was observed on the release of the other transmitters studied. The GABA-releasing action of EGTA was practically abolished in the presence of Mg2+. In contrast, the effect of EDTA was also observed when the medium contained Mg2+. Studies on the ionic dependence showed that the stimulation of GABA release by EGTA was abolished in a Na+-free medium. Li+ did not substitute Na+ for the EGTA effect, which was also independent of chloride. This Na+ dependence does not seem to involve voltage-sensitive channels, since tetrodotoxin did not affect the GABA-releasing action of EGTA, whereas in parallel su-perfusion chambers it blocked over 80% the stimulation of GABA release by veratridine. In contrast, two calcium channel blockers in synaptosomes, La3+ and the cationic dye ruthenium red, greatly inhibited the GABA-releasing effect of EGTA. L-2,4-Diaminobutyric acid, an inhibitor of the Na+-dependent GABA carrier, did not affect the releasing action of EGTA, whereas in a parallel experiment this drug inhibited by more than 90% the exchange of labeled GABA with unlabeled GABA. It is concluded that the Na+-dependent releasing action of EGTA and EDTA on GABA is probably due to a destabilization of the synaptosomal membrane by chelation of endogenous membranal Ca2+, which can be prevented by Mg2+. Such destabilization results in Na+ influx through Ca2+ channels, and the consequent increase in the intrater-minal Na+ concentration induces the release of GABA by a mechanism probably not involving the amino acid carrier. The possible participation of mitochondrial Na+ -Ca2+ exchange is considered improbable in view of the lack of effect of EGTA on the release of other neurotrans-mitters.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.1984.tb12736.x
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