FIGURE 3.

The traditional metabolic coupling hypothesis between neurons and astrocytes during glutamatergic neurotransmission. Glutamate released to the synaptic cleft during glutamatergic neurotransmission is co-transported with Na⁺ to the astrocytes. Astrocytic Na⁺ is exchanged by extracellular K⁺ through the Na⁺/K⁺ ATPase, consuming one ATP molecule. Astrocytic glutamate produces glutamine through glutamine synthetase, consuming one additional ATP molecule. Lactate produced exclusively in astrocytic glycolysis to support these energy demands, is extruded to the extracellular medium, taken up by the surrounding neurons and oxidized as their main metabolic fuel. Note the apparent stoichiometric coupling between glutamate–glutamine cycling and glucose uptake as well as the exclusive glycolytic or oxidative metabolisms in astrocytes and neurons, respectively. Gln, glutamine; Glu, glutamate; GLUT 1 and GLUT 3, glucose transporters 1 and 3; Lac, lactate; MCT1 and MCT2, monocarboxylate transporters 1 and 2; PGK, phosphoglycerate kinase; Pyr, pyruvate. Adapted with permission from Tsacopoulos and Magistretti (1996).