title: Roles of glial glutamate transporters in shaping EPSCs at the climbing fiber-Purkinje cell synapses.
abstract: Glial glutamate transporters, GLAST and GLT-1, are co-localized in processes of Bergmann glia (BG) wrapping excitatory synapses on Purkinje cells (PCs). Although GLAST is expressed six-fold more abundantly than GLT-1, no change is detected in the kinetics of climbing fiber (CF)-mediated excitatory postsynaptic currents (CF-EPSCs) in PCs in GLAST(-/-) mice compared to the wild-type mice (WT). Here we aimed to clarify the mechanism(s) underlying this unexpected finding using a selective GLT-1 blocker, dihydrokainate (DHK), and a novel antagonist of glial glutamate transporter, (2S,3S)-3-[3-(4-methoxybenzoylamino)benzyloxy]aspartate (PMB-TBOA). In the presence of cyclothiazide (CTZ), which attenuates the desensitization of AMPA receptors, DHK prolonged the decay time constant (tau(w)) of CF-EPSCs in WT, indicating that GLT-1 plays a partial role in the removal of glutamate. The application of 100 nM PMB-TBOA, which inhibited CF-mediated transporter currents in BG by approximately 80%, caused no change in tau(w) in WT in the absence of CTZ, whereas it prolonged tau(w) in the presence of CTZ. This prolonged value of tau(w) was similar to that in GLAST(-/-) mice in the presence of CTZ. These results indicate that glial glutamate transporters can apparently retain the fast decay kinetics of CF-EPSCs if a small proportion ( approximately 20%) of functional transporters is preserved.
authors.affiliation: Department of Neurophysiology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan. takatsur@med.gunma-u.ac.jp
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takatsuru
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Takayasu
authors.forename: Masae
authors.initials: M
authors.lastname: Iino
authors.forename: Osamu
authors.initials: O
authors.lastname: Nikkuni
authors.forename: Yuto
authors.initials: Y
authors.lastname: Ueda
authors.forename: Kohichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Seiji
authors.initials: S
authors.lastname: Ozawa
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D015153:Blotting, Western; D027342:Excitatory Amino Acid Transporter 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D050581:Excitatory Amino Acid Transporter 4 / Q000235:genetics / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011690:Purkinje Fibers / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism*
chemical_list: D027322:Amino Acid Transport System X-AG; D027342:Excitatory Amino Acid Transporter 2; D050581:Excitatory Amino Acid Transporter 4; C493390:Slc1a6 protein, mouse; D050496:Vesicular Glutamate Transport Proteins; C120673:benzyloxyaspartate; D001224:Aspartic Acid