Feedback adaptation of synaptic excitability via Glu:Na+ symport driven astrocytic GABA and Gln release. (15th December 2019)

• Record Type: Journal Article
• Authors: Héja, László; Simon, Ágnes; Szabó, Zsolt; Kardos, Julianna
• Is Part Of: Neuropharmacology. Volume 161(2019)
• Publication Date: 2019-12-15
• Subjects: Electrogenic Glu:Na+ symport -- Astrocytic Glu-GABA exchange -- GABA efflux mechanism -- Tonic inhibition -- Neuro-glia synchronization; AD Alzheimer's disease -- EAAT excitatory amino acid transporter -- GAT GABA transporter -- HD Huntington's disease -- NCX Na+/Ca2+ exchanger; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2019.05.006
• Languages: English
• ISSNs: 0028-3908

Abstract

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. This article is part of the issue entitled 'Special Issue on Neurotransmitter Transporters'. Highlights: Astrocytic Glu:Na + symport links inhibition to excitation via GABA release. Astrocytic GABA induces tonic inhibition, rising adaptation at tripartite synapses. Extrasynaptic levels of Glu, GABA and precursor Gln may follow "push-pull" dynamics. Astrocytic GABA release conjectures low-affinity transporter binding of Na + -GABA. Improving synaptic adaptation by astrocytes may relieve several disease conditions.