Further studies on the role of calcium in the regulation of glutamate decarboxylase activity in brain slices.

[3H]GABA synthesis in brain slices was used as a model to study the role of Ca2+ in the regulation of GAD activity. Experimental conditions were chosen to increase and decrease the flux of Ca2+ and to promote the increase in free intracellular Ca2+. The blockade of electron transport and the inhibition of oxidative phosphorylation in the slices inhibited [3H]GABA synthesis. High K+ depolarization stimulated [3H]GABA synthesis and this effect was not blocked by lidocaine, trifluoperazine, or verapamil, but the stimulation was blocked by the intracellular Ca2+ antagonist TMB-8. The data do not differentiate between the relative contributions of extra- and intracellular Ca2+ but reflect that GAD activity is modulated by a dynamic balance between these two compartments as well as between stored and free Ca2+ within the cells.