An excitatory amino-acid transporter with properties of a ligand-gated chloride channel

• Published in: Nature (London) 1995-06, Vol.375 (6532), p.599-603
• Main Authors: Fairman, W. A, Vandenberg, R. J, Arriza, J. L, Kavanaught, M. P, Amara, S. G
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino Acid Transport System X-AG; amino acid transporter; Amino acids; Animals; aspartate/glutamate transporter; Aspartic Acid - metabolism; Base Sequence; Biochemistry; Biochemistry and metabolism; Biological and medical sciences; Brain; cDNA; Cells, Cultured; Central nervous system; cerebellum; Cerebellum - metabolism; chloride channels (ligand-gated); Chloride Channels - genetics; Chloride Channels - metabolism; chloride conductance; Chlorides - metabolism; Cloning; DNA, Complementary; EAAT4 protein; Excitatory Amino Acid Transporter 4; Fundamental and applied biological sciences. Psychology; gene expression; Glutamate Plasma Membrane Transport Proteins; glutamic acid receptors; Humanities and Social Sciences; Humans; Ion Channel Gating; Ions; letter; Ligands; man; Membrane Potentials; Molecular Sequence Data; multidisciplinary; nucleotide sequence; Oocytes - metabolism; Permeability; Receptors, Amino Acid - genetics; Receptors, Amino Acid - metabolism; Receptors, Glutamate - genetics; Receptors, Glutamate - metabolism; Science; Science (multidisciplinary); Sequence Homology, Amino Acid; Sodium - metabolism; Symporters; Vertebrates: nervous system and sense organs; Xenopus
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/375599a0

EXCITATORY amino-acid transporters (EAATs) in the central nervous system maintain extracellular glutamate concentrations below excitotoxic levels and may limit the activation of glutamate receptors. Here we report the cloning of a novel human aspartate/ glutamate transporter, EAAT4, which is expressed predominantly in the cerebellum. The transport activity encoded by EAAT4 has high apparent affinity for L-aspartate and L -glutamate, and has a pharmacological profile consistent with previously described cere-bellar transport activities. In Xenopus oocytes expressing EAAT4, L -aspartate and i -glutamate elicited a current predominantly carried by chloride ions. This chloride conductance was not blocked by components that block endogenous oocyte chloride channels. Thus EAAT4 combines the re-uptake of neurotransmitter with a mechanism for increasing chloride permeability, both of which could regulate excitatory neurotransmission.