GABA

In synaptic vesicles of inhibitory neurons, GABA is locally synthesized mainly by glutamic acid decarboxylase (GAD) and is packaged into vesicles by the vesicular GABA transporter, VGAT. In addition, GABA is recycled from synaptic cleft through membrane GABA transporter, GAT. Glutamate is transported either by EAAC1 (excitatory amino acid carrier-1; EAAT-3) located on GABA neurons or by GLT-1 (glutamate transporter-1; EAAT-2) located on astrocytes. The latter pathway provides an efficient way to recycle glutamate via the glutamate-glutamine cycle. Glutamate, taken up by astrocytes, is converted by glutamine synthetase into glutamine, which is then released and taken up by neuronal system A (SA-1) transporters into GABAergic neurons. Neuronal glutamine then can be converted into glutamate via phosphate activated glutaminase (PAG) in the mitochondria. It is our hypothesis that the astrocytic glutamate-glutamine cycle contributes dynamically to GABA synaptic vesicle refilling.