title: Differential roles of glial and neuronal glutamate transporters in Purkinje cell synapses.
abstract: Glutamate transporters are essential for terminating excitatory neurotransmission. Two distinct glutamate transporters, glutamate-aspartate transporter (GLAST) and excitatory amino acid transporter 4 (EAAT4), are expressed most abundantly in the molecular layer of the cerebellar cortex. GLAST is expressed in Bergmann glial processes surrounding excitatory synapses on Purkinje cell dendritic spines, whereas EAAT4 is concentrated on the extrasynaptic regions of Purkinje cell spine membranes. To clarify the functional significance of the coexistence of these transporters, we analyzed the kinetics of EPSCs in Purkinje cells of mice lacking either GLAST or EAAT4. There was no difference in the amplitude or the kinetics of the rising and initial decay phase of EPSCs evoked by stimulations of climbing fibers and parallel fibers between wild-type and EAAT4-deficient mice. However, long-lasting tail currents of the EPSCs appeared age dependently in most of Purkinje cells in EAAT4-deficient mice. These tail currents were never seen in mice lacking GLAST. In the GLAST-deficient mice, however, the application of cyclothiazide that reduces desensitization of AMPA receptors increased the peak amplitude of the EPSC and prolonged its decay more markedly than in both wild-type and EAAT4-deficient mice. The results indicate that these transporters play differential roles in the removal of synaptically released glutamate. GLAST contributes mainly to uptake of glutamate that floods out of the synaptic cleft at early times after transmitter release. In contrast, the main role of EAAT4 is to remove low concentrations of glutamate that escape from the uptake by glial transporters at late times and thus prevents the transmitter from spilling over to neighboring synapses.
authors.affiliation: Department of Neurophysiology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Takayasu
authors.forename: Masae
authors.initials: M
authors.lastname: Iino
authors.forename: Wataru
authors.initials: W
authors.lastname: Kakegawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maeno
authors.forename: Kei
authors.initials: K
authors.lastname: Watase
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.forename: Dai
authors.initials: D
authors.lastname: Yanagihara
authors.forename: Taisuke
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Okiru
authors.initials: O
authors.lastname: Komine
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kohichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Seiji
authors.initials: S
authors.lastname: Ozawa
mesh_terms: D000818:Animals; D027341:Excitatory Amino Acid Transporter 1 / Q000502:physiology*; D050581:Excitatory Amino Acid Transporter 4 / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D011689:Purkinje Cells / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D050581:Excitatory Amino Acid Transporter 4; C493393:Slc1a3 protein, mouse