Glutamate and potassium stimulation of hippocampal slices metabolizing glucose or glucose and pyruvate

Using 2-deoxyglucose phosphorylation as an index of glucose use and concentrations of selected intermediates to monitor metabolic pathways, responses of rat hippocampal slices to glutamate and K+ stimulation were examined. With glutamate, the glucose phosphorylation rate (GPR) increased, and the slices accumulated glutamate at a constant rate, for 10 min. The uptake rate at each glutamate level was matched, approximately, by the increase in GPR at that level, with 4 or 5 glutamate molecules accumulated for every glucose molecule phosphorylated. Phosphocreatine and ATP levels fell abruptly, and lactate rose, probably reflecting neuronal activity, found by others to be very brief in the presence 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 changes in malate may be the result of the participation of mitochondrial malate dehydrogenase in both citrate cycle and malate shuttle. Citrate and alpha-ketoglutarate rose only with K+. When pyruvate was added to the medium, resting GPR was reduced, but for both stimulants the relative increases in GPR with stimulation were the same as without pyruvate. The changes in metabolic intermediates in response to K+ were like those with glucose alone. But with glutamate, the rise in lactate was greatly diminished, and malate fell instead of rising. Glutamate interference with the transfer of both 3-carbon as well as 4- and 5-carbon intermediates from glia to neurons may explain these results. If so, this interference is greater with pyruvate supplementation than with glucose alone.