EXCITATORY AMINO-ACID TRANSPORTER-5, A RETINAL GLUTAMATE TRANSPORTER COUPLED TO A CHLORIDE CONDUCTANCE

Although a glutamate-gated chloride conductance with the properties of a sodium-dependent glutamate transporter has been described in verteb rate retinal photoreceptors and bipolar cells, the molecular species u nderlying this conductance has not yet been identified. We now report the cloning and functional characterization of a human excitatory amin o acid transporter, EAAT5, expressed primarily in retina. Although EAA T5 shares the structural homologies of the EAAT gene family, one novel feature of the EAAT5 sequence is a carboxy-terminal motif identified previously in N-methyl-D-aspartate receptors and potassium channels an d shown to confer interactions with a family of synaptic proteins that promote ion channel clustering. Functional properties of EAAT5 were e xamined in the Xenopus oocyte expression system by measuring radiolabe led glutamate flux and two-electrode voltage clamp recording. EAAT5-me diated L-glutamate uptake is sodium- and voltage-dependent and chlorid e-independent. Transporter currents elicited by glutamate are also sod ium- and voltage-dependent, but ion substitution experiments suggest t hat this current is largely carried by chloride ions. These properties of EAAT5 are similar to the glutamate-elicited chloride conductances previously described in retinal neurons, suggesting that the EAAT5-ass ociated chloride conductance may participate in visual processing.