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

Nature. 1995 Jun 15;375(6532):599-603. 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 cerebellar transport activities. In Xenopus oocytes expressing EAAT4, L-aspartate and L-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Transport System X-AG*
  • Animals
  • Aspartic Acid / metabolism
  • Base Sequence
  • Cells, Cultured
  • Cerebellum / metabolism*
  • Chloride Channels / genetics
  • Chloride Channels / metabolism*
  • Chlorides / metabolism
  • DNA, Complementary
  • Excitatory Amino Acid Transporter 4
  • Glutamate Plasma Membrane Transport Proteins
  • Humans
  • Ion Channel Gating
  • Ligands
  • Membrane Potentials
  • Molecular Sequence Data
  • Oocytes / metabolism
  • Receptors, Amino Acid / genetics
  • Receptors, Amino Acid / metabolism*
  • Receptors, Glutamate / genetics
  • Receptors, Glutamate / metabolism*
  • Sequence Homology, Amino Acid
  • Sodium / metabolism
  • Symporters*
  • Xenopus


  • Amino Acid Transport System X-AG
  • Chloride Channels
  • Chlorides
  • DNA, Complementary
  • Excitatory Amino Acid Transporter 4
  • Glutamate Plasma Membrane Transport Proteins
  • Ligands
  • Receptors, Amino Acid
  • Receptors, Glutamate
  • SLC1A6 protein, human
  • Symporters
  • aspartic acid receptor
  • Aspartic Acid
  • Sodium

Associated data

  • GENBANK/U18244