High-density presynaptic transporters are required for glutamate removal from the first visual synapse.
Reliable synaptic transmission depends not only on the release machinery and the postsynaptic response mechanism but also on removal or degradation of transmitter from the synaptic cleft. Accumulating evidence indicates that postsynaptic and glial excitatory amino acid transporters (EAATs) contribute to glutamate removal. However, the role of presynaptic EAATs is unclear. Here, we show in the mouse retina that glutamate is removed from the synaptic cleft at the rod to rod bipolar cell (RBC) synapse by presynaptic EAATs rather than by postsynaptic or glial EAATs. The RBC currents evoked by electrical stimulation of rods decayed slowly after pharmacological blockade of EAATs. Recordings of the evoked RBC currents from EAAT subtype-deficient mice and the EAAT-coupled anion current reveal that functional EAATs are localized to rod terminals. Model simulations suggest that rod EAATs are densely packed near the release site and that rods are equipped with an almost self-sufficient glutamate recollecting system.
Hasegawa
Jun
J
Department of Psychology, Graduate School of Humanities and Sociology, The University of Tokyo, Tokyo 113-0033, Japan.
Obara
Takehisa
T
Tanaka
Kohichi
K
Tachibana
Masao
M
D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D027341:Excitatory Amino Acid Transporter 1 / Q000172:deficiency; D050580:Excitatory Amino Acid Transporter 3 / Q000172:deficiency; D050491:Glutamate Plasma Membrane Transport Proteins / Q000502:physiology*; D005971:Glutamates / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009010:Monte Carlo Method; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D010775:Photic Stimulation / Q000379:methods; D017729:Presynaptic Terminals / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology; D012160:Retina / Q000166:cytology; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors
C114785:2-amino-4-phosphono-propinate; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D027341:Excitatory Amino Acid Transporter 1; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D005971:Glutamates; D011422:Propionates; C493399:Slc1a1 protein, mouse; C493393:Slc1a3 protein, mouse; C120673:benzyloxyaspartate; D001224:Aspartic Acid