EXCITATORY amino-acid transporters (EAATs) in the central nervous syst
em maintain extracellular glutamate concentrations below excitotoxic l
evels and may limit the activation of glutamate receptors. Here we rep
ort the cloning of a novel human aspartate/glutamate transporter, EAAT
4, which is expressed predominantly in the cerebellum. The transport a
ctivity encoded by EAAT4 has high apparent affinity for L-aspartate an
d L-glutamate, and has a pharmacological profile consistent with previ
ously described cerebellar transport activities. In Xenopus oocytes ex
pressing EAAT4, L-aspartate and L-glutamate elicited a current predomi
nantly carried by chloride ions. This chloride conductance was not blo
cked by components that block endogenous oocyte chloride channels. Thu
s EAAT4 combines the re-uptake of neurotransmitter with a mechanism fo
r increasing chloride permeability, both of which could regulate excit
atory neurotransmission.