NA+-DEPENDENT GABA TRANSPORT-SYSTEM SCAVENGES ENDOGENOUS EXTERNAL GABA AND PREVENTS DESENSITIZATION OF GABA-A RECEPTORS IN RAT CEREBROCORTICAL SYNAPTONEUROSOMES

Muscimol-induced 36Cl- uptake in rat cerebroctical synaptoneurones was reduced upon exposure of the membrane sacs to low Na+ media. This Na+ requirement led us to examine the role of the Na+-dependent γ-aminobutyric acid (GABA) transport system in 36Cl- uptake. Incubation of the synaptoneurosomes with nipecotic acid, a specific inhibitor of the GABA transport system, for 10 min increased the level of endogenous external GABA from less than 10 to 150 μM and induced the same signs of desensitization as observed with high muscimol-treated synaptoneurosomes; a marked reduction of muscimol-induced 36Cl- uptake and an appearance of a slow bicuculline-sensitive 36Cl- uptake, probably due to a continuous recovery of a population of GABAA receptors from desesitization. Similar results were obtained upon dissipation of Na+ electrochemical gradient across the membranes binhibition of Na+, K+-ATPase with ouabain or by blocking energy metabolism with azide or N-ethylmaleimide. We propose that the Na+-dependent GABA transport system, its operation being dependent on inwardly directed Na+ electrochemical gradient, is responsible for scavenging endogenous GABA released from the synaptoneurosomes, and thus prevents desensitization of GABAA receptors. © 1990.