Release of endogenous GABA can occur through Ca(2+)-dependent and Ca(2+)-independent processes

Release of ?-aminobutyric acid (GABA) can be elicited by electrical field stimulation even in the absence of external Ca(2+). Indeed, the release of GABA under such conditions is even higher than in the presence of Ca(2+). To investigate the underlying mechanism of this phenomenon, the release of endogenous GABA from rat striatal slices was measured by high performance liquid chromatography with electro- chemical detection. Electrical stimulation at 2 Hz for 3 min elevated GABA efflux by 4.5-fold. Withdrawing external Ca(2+) and adding 1 mM EGTA produced a small, transient increase in the basal efflux of GABA and increased electrically-evoked overflow 3-fold. Tetrodotoxin (5 ?M) did not affect basal efflux in either normal or Ca(2+)-free conditions, but abolished electrically-evoked release. In the presence of normal Ca(2+), nipecotic acid (1 mM) enhanced both spontaneous efflux and evoked overflow. Nipecotic acid also increased spontaneous release when external Ca(2+) was removed. However, in the absence of Ca(2+), nipecotic acid failed to increase electrically evoked GABA overflow. These results suggest that there exists a Ca(2+)-independent process for GABA release via the same carrier system that is utilized for high affinity GABA uptake.