The alkaline earths Ca++, Sr++, and Ba++ stimulated the secretion of [14C]γ-aminobutyric acid from isolated brain synaptosomes at various K+ and veratridine concentrations. K+ and veratridine produced different orderings of alkaline earth secretion-stimulation efficacy. In addition, La+++ stimulated release in the presence of either K+ or veratridine. Ca++ concentrations above physiological levels inhibited secretion in the presence of moderately elevated K+ concentrations, but not in Na+-free veratridine solutions. Tetrodotoxin inhibited Ca++-stimulated secretion only when veratridine was present. Mn++ inhibited secretion in the presence of either K+ or veratridine. These results agree well with comparable data from the neuromuscular junction and the adrenal medulla. Consideration of differential membrane permeability to divalent cations and differential interaction of the ions with intracellular binding sites provides a rationale for the relatives efficacies of the alkaline earths.
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