title: The glutamate transporter EAAT5 works as a presynaptic receptor in mouse rod bipolar cells.
abstract: Membrane neurotransmitter transporters control the concentration of their substrate in the synaptic clefts, through the thermodynamic coupling of uptake to the movement of Na(+) and other ions. In addition, excitatory amino acid transporters (EAAT) have a Cl(-) conductance which is gated by the joint binding of Na(+) and glutamate, but thermodynamically uncoupled to the flux of glutamate. This conductance is particularly large in the retina-specific EAAT5 isoform. In the mouse retina, we located EAAT5 in both cone and rod photoreceptor terminals and in axon terminals of rod bipolar cells. In these later cells, application of glutamate on the axon terminal evoked a current that reversed at E(Cl), was insensitive to bicuculline, TPMPA, strychnine, dl-AP5, CNQX and MCPG, but blocked by the glutamate transporter inhibitor dl-tBOA. Furthermore, short depolarizations of the bipolar cells evoked a dl-tBOA and Cd(2+)-sensitive current whose amplitude was comparable to the glutamate-evoked current. Its kinetics indicated that EAAT5 was located close to the glutamate release site. For 2 ms depolarizations evoking maximal responses, the EAAT5-mediated current carried between 2 and 8 times more charge as an average inhibitory GABA or glycine postsynaptic current received spontaneously from amacrine cells, with 10 mm or 0.5 mm intracellular EGTA, respectively. In conditions for which reciprocal inhibition could be monitored, the charge carried by the EAAT5 current was 1.5 times larger than the one carried by the inhibitory postsynaptic currents received from amacrine cells. These results indicate that EAAT5 acts as a major inhibitory presynaptic receptor at mammalian rod bipolar cell axon terminals. This feedback mechanism could control glutamate release at the ribbon synapses of a non-spiking neuron and increase the temporal contrast in the rod photoreceptor pathway.
authors.affiliation: Laboratory of Cellular and Molecular Physiopathology of the Retina, National Institute for Health and Medical Research (INSERM Unité 592), Université Pierre et Marie Curie-Paris6, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Wersinger
authors.forename: Yannick
authors.initials: Y
authors.lastname: Schwab
authors.forename: José-Alain
authors.initials: JA
authors.lastname: Sahel
authors.forename: Alvaro
authors.initials: A
authors.lastname: Rendon
authors.forename: David V
authors.initials: DV
authors.lastname: Pow
authors.forename: Serge
authors.initials: S
authors.lastname: Picaud
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Roux
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D050582:Excitatory Amino Acid Transporter 5 / Q000378:metabolism*; D018698:Glutamic Acid / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D017661:Receptors, Presynaptic / Q000378:metabolism*; D051245:Retinal Bipolar Cells / Q000187:drug effects / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D050582:Excitatory Amino Acid Transporter 5; D017661:Receptors, Presynaptic; D018698:Glutamic Acid