title: Glutamate transporters and metabotropic receptors regulate excitatory neurotransmission in the medial entorhinal cortex of the rat.
abstract: In layer III of the medial entorhinal cortex (mEC), a region that is especially prone to cell damage in Alzheimer's disease, schizophrenia and epilepsy, effects of blocking glutamate uptake on excitatory synaptic transmission were studied. Two competitive glutamate transporter antagonists, TBOA and tPDC, reduced the amplitude of pharmacologically isolated AMPAR and NMDAR mediated EPSPs/EPSCs without changing the time course of the events. This effect was mimicked by tACPD, an agonist of groups I and II metabotropic glutamate receptors (mGluRs). The competitive groups I and II mGluR antagonist MCPG blocked the depression of the EPSC amplitude induced by tACPD and also prevented the effect of either TBOA or tPDC. Furthermore, EGLU, which selectively antagonizes group II mGluRs, blocked the effect of tPDC and LY3414965, a specific group I mGluR antagonist, abolished the reduction of amplitude caused by TBOA. Additionally, application of TBOA increased the paired-pulse index, suggesting a presynaptic mechanism for the depression of EPSP/EPSC amplitude. The present data suggest that glutamate transporters and group I/II mGluRs regulate excitatory synaptic transmission in the mEC. Presynaptic mGluRs may limit excessive glutamate accumulation if uptake becomes compromised.
authors.affiliation: Johannes-Mueller-Institute of Physiology, Dept. of Neurophysiology, Faculty of Medicine (Charité), Humboldt-University, Tucholskystr. 2, 10117 Berlin, Germany. claudia.iserhot@charite.de
authors.forename: Claudia
authors.initials: C
authors.lastname: Iserhot
authors.forename: Christine
authors.initials: C
authors.lastname: Gebhardt
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schmitz
authors.forename: Uwe
authors.initials: U
authors.lastname: Heinemann
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000502:physiology*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004347:Drug Interactions; D018728:Entorhinal Cortex / Q000187:drug effects / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D016202:N-Methylaspartate / Q000494:pharmacology; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014966:Xanthenes / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D027322:Amino Acid Transport System X-AG; D000596:Amino Acids; D003998:Dicarboxylic Acids; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D014179:Neurotransmitter Uptake Inhibitors; D011759:Pyrrolidines; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C120673:benzyloxyaspartate; C474696:methyl-(4-carboxyphenyl)glycine; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C083486:pyrrolidine-2,4-dicarboxylic acid; D005998:Glycine