Sodium-dependent efflux of [3H]GABA from synaptosomes probably related to mitochondrial calcium mobilization.
It has been suggested that mitochondria might modify transmitter release through the control of intracellular Ca2+ levels. Treatments known to inhibit Ca2+ retention by mitochondria lead to an increased transmitter liberation in the absence of external Ca2+, both at the frog neuromuscular junction and from isolated nerve endings. Sodium ions stimulate Ca2+ efflux from mitochondria isolated from excitable tissues. In the present study, the effect of increasing internal Na+ levels on [3H]gamma-aminobutyric acid ([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, gramicidin D, and K+-free medium, which increase the internal sodium 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-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.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000494:pharmacology*; D013574:Synaptosomes / Q000378:metabolism*; D014702:Veratrine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D004533:Egtazic Acid; D005680:gamma-Aminobutyric Acid; D010042:Ouabain; D012964:Sodium; D014702:Veratrine; D011802:Quinidine; D002118:Calcium