Modulation of gamma-aminobutyric acid transport in nerve endings: role of extracellular gamma-aminobutyric acid and of cationic fluxes.
The aim of the present study was to elucidate the possible functional significance of gamma-aminobutyric acid (GABA) homoexchange at nerve endings. Using synaptosomes from adult rat cerebrum, we found that a number of conditions altering cationic fluxes produced a concomitant change in the stoichiometry of GABA homoexchange, In fact, exogenous GABA (10 muM), while not causing net release of intrasynaptosomal GABA in standard conditions, triggered a large net GABA release in the presence of veratridine, Na(+)-K(+)-ATPase inhibitors, or the ionophore A23187, superimposed on that due to the various agents tested alone. This extra release was mediated by the membrane carrier, being largely inhibited by the GABA carrier-blocker L-diaminobutyric acid. The altered stoichiometry of GABA homoexchange observed under these conditions (efflux > influx) appeared to be coupled to the influx of Na(+) (or of Ca(2+)), rather than determined by the establishment of a high intrasynaptosomal [Na(+)]. Under conditions of reversed Na(+) flux (Na(+) efflux), the GABA outward/inward flux ratio was also reversed, and the stoichiometry of GABA homoexchange was in favor of net influx. The possible contribution of K(+) to the effects observed is also discussed. It is concluded that the GABA transport system of nerve endings is susceptible to fine modulation by changes in cationic fluxes similar to those occurring in vivo during depolarization and repolarization. These fluxes may have a prominent role in determining the direction of net GABA transport in GABA-ergic nerve terminals of the living brain.
D000613:Aminobutyrates / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D009411:Nerve Endings / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000613:Aminobutyrates; D000001:Calcimycin; D005680:gamma-Aminobutyric Acid; D012964:Sodium; D002118:Calcium