GABA efflux from synaptosomes: Effects of membrane potential, and external GABA and cations

Mark T. Nelson, Mordecai P. Blaustein

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Presynaptic GABAergic nerve terminals accumulate γ-aminobutyric acid (GABA) by a sodium-dependent carrier mechanism in which two Na+ are co-transported with one GABA. We have examined the influence of external GABA and cations on GABA efflux from3H-GABA loaded rat brain synaptosomes, to determine whether or not the carriers can also mediate GABA efflux. We observed that, in Ca-free media (to minimize Ca-dependent evoked release), external GABA promotes GABA efflux when the medium contains Na+, but inhibits GABA efflux in the absence of Na+. The efflux of GABA into Ca-free media is stimulated by depolarization (either with veratridine or increased external K+). These data, and published data on the internal Na+ dependence of GABA efflux into Ca-free media, indicate that exiting GABA is cotransported with Na+. The stimulatory effect of depolarization is consistent with efflux of Na+ along with the uncharged GABA. The (carrier-mediated) efflux is also stimulated when the carriers cycle inward with Na++GABA. The inhibitory effect of GABA in Na+-free media implies that GABA can bind to unloaded carriers and that the carriers loaded only with GABA cycle very slowly, if at all. Our data, and data from the literature, can be fitted to a simple model with sequential binding of solutes: external GABA binds to the carrier first, and only the free or fully-loaded (with 2Na++1GABA) carriers can cycle. Other binding sequences and random binding, do not fit the experimental observations. © 1982 Springer-Verlag New York Inc.
    Original languageEnglish
    Pages (from-to)213-223
    Number of pages10
    JournalJournal of Membrane Biology
    Volume69
    Issue number3
    DOIs
    Publication statusPublished - Oct 1982

    Keywords

    • carrier-mediated transport
    • GABA
    • gamma-aminobutyric acid
    • presynaptic nerve terminals
    • sodium-GABA co-transport
    • synaptosomes

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