title: Neuronal glutamate transporters vary in substrate transport rate but not in unitary anion channel conductance.
abstract: Excitatory amino acid transporters (EAATs) not only sustain a secondary active glutamate transport but also function as anion-selective ion channels. The relative proportion of currents generated by glutamate transport or by the chloride conductance varies for each cloned EAAT subtype. For EAAT1, EAAT2, and EAAT3, the anion current is only a small component of the total transporter-associated current amplitude, whereas EAAT4 and EAAT5 transporters mediate predominantly anion currents. We here demonstrate that the distinct current proportions are entirely due to differences in glutamate transport rates. EAAT3 and EAAT4 differ in unitary glutamate transport rates as well as in the voltage and substrate dependence of anion channel opening, but ion conduction properties are very similar. Noise analysis revealed identical unitary current amplitudes and similar absolute open probabilities for the two anion channels. The low glutamate transport rate of EAAT4 allows regulation of cellular excitability without interfering with extracellular glutamate homeostasis and makes this EAAT isoform ideally suited to regulate excitability in dendritic spines of Purkinje neurons.
authors.affiliation: Institut für Neurophysiologie, Medizinische Hochschule, D-30625 Hannover, Germany.
authors.forename: Delany
authors.initials: D
authors.lastname: Torres-Salazar
authors.forename: Christoph
authors.initials: C
authors.lastname: Fahlke
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D003712:Dendrites / Q000378:metabolism; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism / Q000502:physiology*; D050581:Excitatory Amino Acid Transporter 4 / Q000378:metabolism / Q000502:physiology*; D050582:Excitatory Amino Acid Transporter 5 / Q000378:metabolism; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism; D006801:Humans; D007477:Ions; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011336:Probability; D020033:Protein Isoforms; D011689:Purkinje Cells / Q000378:metabolism; D014981:Xenopus
chemical_list: D027322:Amino Acid Transport System X-AG; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D050581:Excitatory Amino Acid Transporter 4; D050582:Excitatory Amino Acid Transporter 5; D050491:Glutamate Plasma Membrane Transport Proteins; D007477:Ions; D020033:Protein Isoforms; C493400:SLC1A1 protein, human; C493397:SLC1A2 protein, human; C493394:SLC1A3 protein, human; C493391:SLC1A6 protein, human; C105645:SLC1A7 protein, human