Feedback adaptation of synaptic excitability via Glu:Na+ symport driven astrocytic GABA and Gln release

Abstract Glutamatergic transmission composed of the arriving of action potential at the axon terminal, fast vesicular Glu release, postsynaptic Glu receptor activation, astrocytic Glu clearance and Glu→Gln shuttle is an abundantly investigated phenomenon. Despite its essential role, however, much less is known about the consequences of the mechanistic connotations of Glu:Na + symport. Due to the coupled Na + transport, Glu uptake results in significantly elevated intracellular astrocytic [Na + ] that markedly alters the driving force of other Na + -coupled astrocytic transporters. The resulting GABA and Gln release by reverse transport through the respective GAT-3 and SNAT3 transporters help to re-establish the physiological Na + homeostasis without ATP dissipation and consequently leads to enhanced tonic inhibition and replenishment of axonal glutamate pool. Here, we place this emerging astrocytic adjustment of synaptic excitability into the centre of future perspectives.