(a) Under physiological conditions extracellular glutamate (GLU) is recycled via the concerted work of glutamate uptake via GLAST-1 and GLT-1 transporters, conversion to glutamine (GLN) by glutamine synthetase (GS), and glutamine release and uptake by astrocytic SNAT-3 and neuronal SNAT-1. In neurons, glutamine is hydrolyzed to glutamate by phosphate-activated glutaminase (PAG). (b) Astrocytic cell swelling opens the glutamate-permeable channel VRAC and strongly inhibits activity of GS, resulting in lower levels of glutamine production and export. Other abbreviations: AMPA, NMDA, KA, ionotropic glutamate receptors; α-KG, α-ketoglutarate; GDH, glutamate dehydrogenase; vGluT, vesicular glutamate transporters. Note that for simplicity this diagram omits a number of alternative glutamine transporters and important metabolic enzymes.