title: Intracellular Na+ concentration influences short-term plasticity of glutamate transporter-mediated currents in neocortical astrocytes.
abstract: 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.
authors.affiliation: Institute of Physiology and Pathophysiology, Universal Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Petr
authors.initials: P
authors.lastname: Unichenko
authors.forename: Olga
authors.initials: O
authors.lastname: Myakhar
authors.forename: Sergei
authors.initials: S
authors.lastname: Kirischuk
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D000840:Anisoles / Q000494:pharmacology; D001224:Aspartic Acid / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001572:Benzofurans / Q000378:metabolism; D001703:Biophysics; D019256:Cadmium Chloride / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004558:Electric Stimulation; D004988:Ethers, Cyclic / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000166:cytology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009557:Nipecotic Acids / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D012235:Rhodamines / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
chemical_list: C092337:1-(2-(tris(4-methoxyphenyl)methoxy)ethyl)-3-piperidinecarboxylic acid; D027322:Amino Acid Transport System X-AG; D000840:Anisoles; D001572:Benzofurans; D002121:Calcium Channel Blockers; D004988:Ethers, Cyclic; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D009557:Nipecotic Acids; D010091:Oximes; D012235:Rhodamines; D026941:Sodium Channel Blockers; C120673:benzyloxyaspartate; C061665:sodium-binding benzofuran isophthalate; C078793:NNC 711; D001224:Aspartic Acid; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D012964:Sodium; C050829:sulforhodamine 101; D019256:Cadmium Chloride