GLUTAMATE AND POTASSIUM STIMULATION OF HIPPOCAMPAL SLICES METABOLIZING GLUCOSE OR GLUCOSE AND PYRUVATE

Using 2-deoxyglucose phosphorylation as an index of glucose use and co ncentrations of selected intermediates to monitor metabolic pathways, responses of rat hippocampal slices to glutamate and K+ stimulation we re examined. With glutamate, the glucose phosphorylation rate (GPR) in creased, and the slices accumulated glutamate at a constant rate, for 10 min. The uptake rate at each glutamate level was matched, approxima tely, by the increase in GPR at that level, with 4 or 5 glutamate mole cules accumulated for every glucose molecule phosphorylated. Phosphocr eatine and ATP levels fell abruptly, and lactate rose, probably reflec ting neuronal activity, found by others to be very brief in the presen ce of glutamate. K+ stimulation produced responses of phosphocreatine, ATP and lactate levels and of GPR similar to those due to glutamate. There were also prolonged changes in the levels of other metabolites: with both stimulants glucose 6-phosphate fell, and malate rose. The ch anges in malate may be the result of the participation of mitochondria l malate dehydrogenase in both citrate cycle and malate shuttle. Citra te and alpha-ketoglutarate rose only with K+, When pyruvate was added to the medium, resting GPR was reduced, but for both stimulants the re lative increases in GPR with stimulation were the same as without pyru vate. The changes in metabolic intermediates in response to K+ were Li ke those with glucose alone. But with glutamate, the rise in lactate w as greatly diminished, and malate fell instead of rising. Glutamate in terference with the transfer of both 3-carbon as well as 4- and 5-carb on intermediates from glia to neurons may explain these results. If so , this interference is greater with pyruvate supplementation than with glucose alone.