Glial and Neuronal Glutamate Transporters Differ in the Na+ Requirements for Activation of the Substrate-Independent Anion Conductance
| Autor: | Susan G. Amara, Jon W. Johnson, Jenna E. Borowski, Christopher B. Divito, Delany Torres-Salazar, Nathan G. Glasgow, Aneysis D. Gonzalez-Suarez |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Neurotransmitter transporter neurotransmitter transporters glutamate excitatory amino acid transporter lcsh:RC321-571 03 medical and health sciences Cellular and Molecular Neuroscience Molecular Biology lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Original Research chemistry.chemical_classification Glutamate receptor Glutamate binding Transporter Anion channel activity electrophysiology Amino acid 030104 developmental biology Biochemistry chemistry chloride channels Chloride channel Biophysics Excitatory postsynaptic potential Neuroscience |
| Zdroj: | Frontiers in Molecular Neuroscience, Vol 10 (2017) Frontiers in Molecular Neuroscience |
| ISSN: | 1662-5099 |
| DOI: | 10.3389/fnmol.2017.00150/full |
| Popis: | Excitatory amino acid transporters (EAATs) are secondary active transporters of L-glutamate and L- or D-aspartate. These carriers also mediate a thermodynamically uncoupled anion conductance that is gated by Na+ and substrate binding. The activation of the anion channel by binding of Na+ alone, however, has only been demonstrated for mammalian EAAC1 (EAAT3) and EAAT4. To date, no difference has been observed for the substrate dependence of anion channel gating between the glial, EAAT1 and EAAT2, and the neuronal isoforms EAAT3, EAAT4 and EAAT5. Here we describe a difference in the Na+-dependence of anion channel gating between glial and neuronal isoforms. Chloride flux through transporters without glutamate binding has previously been described as substrate-independent or “leak” channel activity. Choline or N-methyl-D-glucamine replacement of external Na+ ions significantly reduced or abolished substrate-independent EAAT channel activity in EAAT3 and EAAT4 yet has no effect on EAAT1 or EAAT2. The interaction of Na+ with the neuronal carrier isoforms was concentration dependent, consistent with previous data. The presence of substrate and Na+-independent open states in the glial EAAT isoforms is a novel finding in the field of EAAT function. Our results reveal an important divergence in anion channel function between glial and neuronal glutamate transporters and highlight new potential roles for the EAAT-associated anion channel activity based on transporter expression and localization in the central nervous system. |
| Databáze: | OpenAIRE |
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