Flux of substrate and charge mediated by three cloned excitatory amino acid transporters widely expressed in human brain were studied in voltage-clamped Xenopus oocytes. Superfusion of l-glutamate or d-aspartate resulted in currents due in part to electrogenic Na+ cotransport, which contributed 1 net positive charge per transport cycle. A significant additional component of the currents was due to activation of a reversible anion flux that was not thermodynamically coupled to amino acid transport. The selectivity sequence of this ligand-activated conductance was NO3− > I− > Br− > Cl− > F−. The results suggest that these proteins mediate both transporter- and channel-like modes of permeation, providing a potential mechanism for dampening cell excitability, in addition to removal of transmitter.
