High K+-induced Increase in Extracellular Glutamate in Zinc Deficiency and Endogenous Zinc Action

Abstract

To understand the physiological significance of endogenous zinc release under excess excitation in the hippocampus, in the present study, high K + -induced increase in extracellular glutamate and endogenous zinc action against its increase were examined in young rats fed a zinc-deficient diet for 2 weeks. When the ventral hippocampus was perfused by 100 mM KCl, the extracellular concentration of glutamate was more increased in zinc-deficient rats than the control rats. Calcium orange signal in mossy fiber boutons was more increased in slices from zincdeficient rats after delivery of tetanic stimuli (100 Hz, 5 sec) to the dentate granule cell layer. The decrease in FM4-64 signal, which is a measurement of exocytosis, in mossy fiber boutons was also enhanced in slices from zinc-deficient rats. These results suggest that the abnormal increase in extracellular glutamate in the hippocampus induced with high K + in zinc deficiency is due to th ee nhancement of exocytosis associated with affected Ca 2+ mobilization. The expression of GLT-1, a glial glutamate transporter, in the hippocampus was higher in zincdeficient rats, suggesting that GLT-1 protein increased serves to maintain the basal concentration of extracellular glutamate, which was not different between the control and zinc-deficient rats. On the other hand, the increase in extracellular glutamate concentration induced with high K + was enhanced in the presence of 1 mM CaEDTA, a membrane-impermeable zinc chelator, in both the control and zinc-deficient rats. It is likely that zinc released from glutamatergic neurons serves to suppress glutamate release under excess excitation in the hippocampus.