title: Functional diversity of excitatory amino acid transporters: ion channel and transport modes.
abstract: Recent studies of glutamate transporters in the central nervous system indicate that in addition to their fundamental role in mediating neurotransmitter uptake, these proteins may contribute to the modulation of a variety of cellular processes. Activation of the excitatory amino acid (EAA) carriers generates an electrogenic current attibutable to ion-coupled cotransport. In addition to this transport-associated current, a substrate-gated thermodynamically uncoupled anion flux has been identified that has been proposed to dampen neuronal excitability. Arachidonic acid has been reported to modulate a variety of membrane proteins involved in cellular signaling. Here we discuss recent findings that indicate arachidonic acid stimulates a previously uncharacterized proton-selective conductance in the Purkinje cell-specific subtype, EAAT4. The unique channel-like porperties of the EAATs, their unexpected localization, and physiological evidence propose a modulatory role for the EAATs in neuronal signaling and suggest a broader role for glutamate transporters than simply the clearance of synaptically released glutamate. Thus, the identification of this arachidonate-stimulated proton conductance extends the complexity of mechanisms through which glutamate transporters modulate neuronal excitability.
authors.affiliation: Howard Hughes Medical Institute, Vollum Institute for Advanced Biomedical Research, Portland, Oregon 97201, USA.
authors.forename: W A
authors.initials: WA
authors.lastname: Fairman
authors.forename: S G
authors.initials: SG
authors.lastname: Amara
mesh_terms: D027322:Amino Acid Transport System X-AG; D026905:Amino Acid Transport Systems; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D004553:Electric Conductivity; D050491:Glutamate Plasma Membrane Transport Proteins; D007473:Ion Channels / Q000378:metabolism; D011522:Protons; D017470:Receptors, Glutamate / Q000378:metabolism / Q000502:physiology; D027981:Symporters
chemical_list: D027322:Amino Acid Transport System X-AG; D026905:Amino Acid Transport Systems; D002352:Carrier Proteins; D050491:Glutamate Plasma Membrane Transport Proteins; D007473:Ion Channels; D011522:Protons; D017470:Receptors, Glutamate; D027981:Symporters; D016718:Arachidonic Acid