Potentiation by K+ of anoxic release of newly synthesized neuronal glutamate

GLUTAMATE synthesis from [C-14]glutamine release of newly synthesized, labelled glutamate and cell death in primary cultures of the glutamatergic cerebellar granule cell neurones under anoxic conditions were increased by an elevation of the extracellular potassium concentration. Phenylsuccinate, an inhibitor of transmitochondrial transport and hence of glutamate synthesis from glutamine, decreased the potassium-enhanced glutamate synthesis and the release of newly synthesized glutamate and reduced cell death. Since the extracellular concentration of potassium is elevated during brain anoxia and glutamate neurotoxicity is thought to contribute to neuronal cell death under this condition, these observations may be of functional and potentially therapeutic relevance.