GLUTAMATE UPTAKE INTO ASTROCYTES STIMULATES AEROBIC GLYCOLYSIS - A MECHANISM COUPLING NEURONAL-ACTIVITY TO GLUCOSE-UTILIZATION

Glutamate, released at a majority of excitatory synapses in the centra l nervous system, depolarizes neurons by acting at specific receptors. Its action is terminated by removal from the synaptic cleft mostly vi a Na+-dependent uptake systems located on both neurons and astrocytes. Here we report that glutamate, in addition to its receptor-mediated a ctions on neuronal excitability, stimulates glycolysis-i.e., glucose u tilization and lactate production-in astrocytes. This metabolic action is mediated by activation of a Naf-dependent uptake system and not by interaction with receptors. The mechanism involves the Na+/K+-ATPase, which is activated by an increase in the intracellular concentration of Na+ cotransported with glutamate by the electrogenic uptake system. Thus, when glutamate is released from active synapses and taken up by astrocytes, the newly identified signaling pathway described here wou ld provide a simple and direct mechanism to tightly couple neuronal ac tivity to glucose utilization. In addition, glutamate-stimulated glyco lysis is consistent with data obtained from functional brain imaging s tudies indicating local nonoxidative glucose utilization during physio logical activation.