Pentylenetetrazole-induced seizure activity produces an increased release of calcium from endoplasmic reticulum by mediating cyclic AMP-dependent protein phosphorylation in rat cerebral cortex.

1. To determine the involvement of the convulsant agent pentylenetetrazole (PTZ) in intracellular calcium release in neurons, its effect on stored calcium in the endoplasmic reticulum of rat cortical neurons was tested. 2. Intraperitoneal injection of PTZ caused marked release of calcium from the endoplasmic reticulum which was similar to that observed when cortical slices were incubated with this convulsant. 3. Superfusion of dibutyryl cAMP and isobutylmethylxanthine to the cortical slices mimicked PTZ-induced calcium release from this reservoir. A similar effect was observed under depolarizing conditions brought about by either an elevation of extracellular K+ concentration or addition of veratridine. 4. Isoquinolinesulfonamide, a protein kinase inhibitor, reduced PTZ-stimulatory effect of calcium release and blocked the cAMP-induced calcium release. 5. Intracellular cAMP level was enhanced at about 3-fold by both intraperitoneal injection of PTZ and its superfusion. 6. These findings are taken to suggest that PTZ may release stored calcium in the endoplasmic reticulum by mediating a cAMP-dependent protein phosphorylation in cortical neurons.