title: Membrane currents and cytoplasmic sodium transients generated by glutamate transport in Bergmann glial cells.
abstract: Effects of glutamate and kainate (KA) on Bergmann glial cells were investigated in mouse cerebellar slices using the whole-cell configuration of the patch-clamp technique combined with SBFI-based Na(+) microfluorimetry. L-glutamate (1 mM) and KA (100 microM) induced inward currents in Bergmann glial cells voltage-clamped at -70 mV. These currents were accompanied by an increase in intracellular Na+ concentration ([Na+](i)) from the average resting level of 5.2 +/- 0.5 mM to 26 +/- 5 mM and 33 +/- 7 mM, respectively. KA-evoked signals (1) were completely blocked in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM), an antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/KA ionotropic glutamate receptors; (2) reversed at 0 mV, and (3) disappeared in Na+ -free, N-methyl-D-glucamine (NMDG+)-containing solution, but remained almost unchanged in Na+ -free, Li+ -containing solution. Conversely, L-glutamate-induced signals (1) were marginally CNQX sensitive (approximately 10% inhibition), (2) did not reverse at a holding potential of +20 mV, (3) were markedly suppressed by Na+ substitution with both NMDG+ and Li+, and (4) were inhibited by D,L-threo-beta-benzyloxyaspartate. Further, D-glutamate, L -, and D-aspartate were also able to induce Na+ -dependent inward current. Stimulation of parallel fibres triggered inward currents and [Na+](i) transients that were insensitive to CNQX and MK-801; hence, we suggested that synaptically released glutamate activates glutamate/Na+ transporter in Bergmann glial cells, which produces a substantial increase in intracellular Na+ concentration.
authors.affiliation: Max-Delbruck-Centre for Molecular Medicine, Robert-Rossle-Strasse 10, 13122 Berlin-Buch, Germany.
authors.forename: Sergei
authors.initials: S
authors.lastname: Kirischuk
authors.forename: Helmut
authors.initials: H
authors.lastname: Kettenmann
authors.forename: Alexei
authors.initials: A
authors.lastname: Verkhratsky
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D009412:Nerve Fibers / Q000502:physiology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
chemical_list: D027322:Amino Acid Transport System X-AG; D018691:Excitatory Amino Acid Antagonists; D019831:Sodium-Calcium Exchanger; C120673:benzyloxyaspartate; D001224:Aspartic Acid; C047635:N-methylglucosamine; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D008094:Lithium; D012964:Sodium; D005944:Glucosamine; D007608:Kainic Acid; D002118:Calcium