Tetanus toxin treatment in vitro inhibits the release of GABA from rat cerebral cortex slices evoked by high K(+) and Na(+)-free media.

The influence of tetanus toxin in vitro on the release of exogenous [(3)H]GABA was studied with rat cerebral cortex slices. The influx, long-term accumulation and spontaneous efflux of GABA were not modified by the toxin. The release induced by high K(+) (50 mM) medium from the superfused slices pretreated with the toxin was significantly inhibited in a time- and dose-dependent fashion. This release was attenuated during superfusion with Ca(2+)-free medium and the toxin no longer affected the remaining Ca(2+)-independent release. The release induced by Na(+)-free media did not require extracellular Ca(2+) ions, and the toxin inhibited the release both with and without Ca(2+). The toxin treatment had no marked influence on the ouabain (20 ?M) or veratrine (25-50 ?M)-induced release of GABA. The toxin treatment in vitro appears to modify some step(s) in the stimulated release of GABA without affecting its unstimulated membrane transport. Tetanus toxin may thus prove a valuable tool in studying the mechanisms of the release of GABA and possibly other inhibitory transmitters in synapses of the central nervous system.