PMID- 22279011 OWN - NLM STAT- MEDLINE DCOM- 20120612 LR - 20161125 IS - 1098-1136 (Electronic) IS - 0894-1491 (Linking) VI - 60 IP - 4 DP - 2012 Apr TI - Intracellular Na+ concentration influences short-term plasticity of glutamate transporter-mediated currents in neocortical astrocytes. PG - 605-14 LID - 10.1002/glia.22294 [doi] AB - Fast synaptic transmission requires a rapid clearance of the released neurotransmitter from the extracellular space. Glial glutamate transporters (excitatory amino acid transporters, EAATs) strongly contribute to glutamate removal. In this work, we investigated the paired-pulse plasticity of synaptically activated, glutamate transporter-mediated currents (STCs) in cortical layer 2/3 astrocytes. STCs were elicited by local electrical stimulation in layer 4 in the presence of ionotropic glutamate (AMPA and NMDA), GABAA, and GABAB receptor antagonists. In experiments with low [Na(+)]i (5 mM) intrapipette solution, STCs elicited by paired-pulse stimulation demonstrated paired-pulse facilitation (PPF) at short (<250 ms) interstimulus intervals (ISIs) and paired-pulse depression at longer ISIs. In experiments with close to physiological, high [Na(+)]i (20 mM) intrapipette solution, PPF of STCs at short ISIs was significantly reduced. In addition, the STC kinetics was slowed in the presence of high [Na(+)]i. Exogenous GABA increased astrocytic [Na(+)]i, reduced the mean STC amplitude, decreased PPF at short ISIs, and slowed STC kinetics. All GABA-induced changes were blocked by NO-711 and SNAP-5114, GABA transporter (GATs) antagonists. In experiments with the low intrapipette solution, GAT blockade under control conditions decreased PPF at short ISIs both at room and at near physiological temperatures. Dialysis of single astrocyte with low [Na(+)]i solution increased the amplitude and reduced PPR of evoked field potentials recorded in the vicinity of the astrocyte. We conclude that (1) endogenous GABA via GATs may influence EAAT functioning and (2) astrocytic [Na(+)]i modulates the short-term plasticity of STCs and in turn the efficacy of glutamate removal. CI - Copyright (c) 2012 Wiley Periodicals, Inc. FAU - Unichenko, Petr AU - Unichenko P AD - Institute of Physiology and Pathophysiology, Universal Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. FAU - Myakhar, Olga AU - Myakhar O FAU - Kirischuk, Sergei AU - Kirischuk S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120125 PL - United States TA - Glia JT - Glia JID - 8806785 RN - 0 (1-(2-(tris(4-methoxyphenyl)methoxy)ethyl)-3-piperidinecarboxylic acid) RN - 0 (Amino Acid Transport System X-AG) RN - 0 (Anisoles) RN - 0 (Benzofurans) RN - 0 (Calcium Channel Blockers) RN - 0 (Ethers, Cyclic) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (GABA Antagonists) RN - 0 (Nipecotic Acids) RN - 0 (Oximes) RN - 0 (Rhodamines) RN - 0 (Sodium Channel Blockers) RN - 0 (benzyloxyaspartate) RN - 124549-08-2 (sodium-binding benzofuran isophthalate) RN - 145645-62-1 (NNC 711) RN - 30KYC7MIAI (Aspartic Acid) RN - 4368-28-9 (Tetrodotoxin) RN - 56-12-2 (gamma-Aminobutyric Acid) RN - 9NEZ333N27 (Sodium) RN - FX0ES3271V (sulforhodamine 101) RN - J6K4F9V3BA (Cadmium Chloride) SB - IM MH - Action Potentials/drug effects/physiology MH - Amino Acid Transport System X-AG/antagonists & inhibitors/*metabolism MH - Animals MH - Animals, Newborn MH - Anisoles/pharmacology MH - Aspartic Acid/pharmacology MH - Astrocytes/drug effects/*physiology MH - Benzofurans/metabolism MH - Biophysics MH - Cadmium Chloride/pharmacology MH - Calcium Channel Blockers/pharmacology MH - Electric Stimulation MH - Ethers, Cyclic/metabolism MH - Excitatory Amino Acid Antagonists/pharmacology MH - GABA Antagonists/pharmacology MH - In Vitro Techniques MH - Intracellular Fluid/drug effects/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Neocortex/*cytology MH - Neuronal Plasticity/drug effects/*physiology MH - Nipecotic Acids/pharmacology MH - Oximes/pharmacology MH - Patch-Clamp Techniques MH - Rhodamines/metabolism MH - Sodium/*metabolism MH - Sodium Channel Blockers/pharmacology MH - Synaptic Transmission/drug effects MH - Tetrodotoxin/pharmacology MH - gamma-Aminobutyric Acid/metabolism/pharmacology EDAT- 2012/01/27 06:00 MHDA- 2012/06/13 06:00 CRDT- 2012/01/27 06:00 PHST- 2011/03/08 00:00 [received] PHST- 2011/12/20 00:00 [accepted] PHST- 2012/01/27 06:00 [entrez] PHST- 2012/01/27 06:00 [pubmed] PHST- 2012/06/13 06:00 [medline] AID - 10.1002/glia.22294 [doi] PST - ppublish SO - Glia. 2012 Apr;60(4):605-14. doi: 10.1002/glia.22294. Epub 2012 Jan 25.