Sodium‐Dependent Efflux of [3H]GABA from Synaptosomes Probably Related to Mitochondrial Calcium Mobilization

Abstract

Mitochondria may modify transmitter release through the control of intracellular Ca2+ levels. Treatments which inhibit Ca2+ retention by mitochondria lead to an increased transmitter liberation in the absence of external Ca2+, at the frog neuromuscular junction and from isolated nerve endings. Na+ stimulate Ca2+ efflux from mitochondria isolated from excitable tissues. In the present study, the effect of increasing internal Na+ levels on [3H]GABA release from isolated nerve endings is reported. Results show that the efflux of [3H]GABA from prelabeled synaptosomes is stimulated by ouabain, veratrine [veratridine], gramicidin D and K+-free medium, which increase the internal Na+ concentration. This effect was not observed when Na+ was omitted from the incubation medium, and it was independent of external Ca2+, the experiments having been performed in a Ca2+-free, EGTA[ethyleneglycol-bis(beta-aminoethyl ether) N,N,N'',N''-tetraacetic acid]-containing medium. Since preincubation of synaptosomes with 2,4-diaminobutyric acid did not prevent the stimulatory effect of increased internal Na+ levels on [3H]GABA efflux, it appears to be unrelated to an enhanced activity of the outward carrier-mediated GABA transport. These results suggest that the augmented release of [3H]GABA may be due to an increased Ca2+ efflux from mitochondria elicited by the accumulation of Na+ at the nerve endings.