THE EFFECT OF ELECTRICAL STIMULATION AND HIGH POTASSIUM CONCENTRATIONS ON THE EFFLUX OF [³H] γ‐AMINOBUTYRIC ACID FROM BRAIN SLICES

Brain slices were incubated with [ 3 H]GABA in a medium containing aminooxyacetic acid to prevent metabolism of [ 3 H]GABA by GABA‐glutamate transaminase. The slices, which rapidly accumulated radioactivity, were then continuously perfused and the efflux of [ 3 H]GABA from the tissue was measured. The spontaneous efflux of [ 3 H]GABA consisted of an initial rapid phase followed by a much slower release of [ 3 [H]GABA. After 40 min perfusion 90 per cent of the radioactivity remained in the tissue. The slices were depolarized by electrical stimulation or by perfusion with a medium containing a high potassium concentration (40 mM). These procedures caused a striking increase in the efflux of [ 3 H]GABA. The increased efflux produced by potassium, but not that produced by electrical stimulation, was dependent on calcium ions in the medium. The effect of electrical stimulation on [ 3 H]GABA release was considerably reduced by a raised concentration (10 mM) of magnesium in the medium. High potassium concentrations and electrical stimulation did not cause an increase in the efflux of [ 14 C]urea, L‐[ 3 H]leucine or [ 14 C]α‐amino‐isobutyric acid from brain slices. These results are consistent with the suggestion that GABA may be an inhibitory transmitter in the cerebral cortex.