ArticleThe Journal of membrane biology2015
Evidence for a Revised Ion/Substrate Coupling Stoichiometry of GABA Transporters.
Article in The Journal of membrane biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Cryo-EM structure of GABA transporter 1 reveals substrate recognition and transport mechanism.Nature structural & molecular biology · 2023Article
- A comparative review on the well-studied GAT1 and the understudied BGT-1 in the brain.Frontiers in physiology · 2023Review
- Flux coupling, not specificity, shapes the transport and phylogeny of SLC6 glycine transporters.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Neuronal activity drives pathway-specific depolarization of peripheral astrocyte processes.Nature neuroscience · 2022Article
- Reconstitution of GABA, Glycine and Glutamate Transporters.Neurochemical research · 2022Review
- The Lepidopteran KAAT1 and CAATCH1: Orthologs to Understand Structure-Function Relationships in Mammalian SLC6 Transporters.Neurochemical research · 2022Article
- GABAergic Mechanisms Can Redress the Tilted Balance between Excitation and Inhibition in Damaged Spinal Networks.Molecular neurobiology · 2021Review
- Heteromeric Solute Carriers: Function, Structure, Pathology and Pharmacology.Advances in experimental medicine and biology · 2021Review
- Glycine Transporter 2: Mechanism and Allosteric Modulation.Frontiers in molecular biosciences · 2021Review
- Mapping of Ion and Substrate Binding Sites in Human Sodium Iodide Symporter (hNIS).Journal of chemical information and modeling · 2020Article
- Modeling and Simulation ofComputational and structural biotechnology journal · 2019Article
- Physiology of Astroglia.Physiological reviews · 2018Review
- Modification of a Putative Third Sodium Site in the Glycine Transporter GlyT2 Influences the Chloride Dependence of Substrate Transport.Frontiers in molecular neuroscience · 2018Article
- Cell Volume Control in Healthy Brain and Neuropathologies.Current topics in membranes · 2018Review
- An Extra Amino Acid Residue in Transmembrane Domain 10 of the γ-Aminobutyric Acid (GABA) Transporter GAT-1 Is Required for Efficient Ion-coupled Transport.The Journal of biological chemistry · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Plasma membrane γ-aminobutyric acid (GABA) transporters (GATs) are electrogenic transport proteins that couple the cotranslocation of Na(+), Cl(-), and GABA across the plasma membrane of neurons and glia. A fundamental property of the transporter that determines its ability to concentrate GABA in cells and, hence, regulate synaptic and extra-synaptic GABA concentrations, is the ion/substrate coupling stoichiometry. Here, we scrutinized the currently accepted 2 Na(+):1 Cl(-):1 GABA stoichiometry because it is inconsistent with the measured net charge translocated per co-substrate (Na(+), Cl(-), and GABA). We expressed GAT1 and GAT3 in Xenopus laevis oocytes and utilized thermodynamic and uptake under voltage-clamp measurements to determine the stoichiometry of the GABA transporters. Voltage-clamped GAT1-expressing oocytes were internally loaded with GABA, and the reversal potential (V rev) of the transporter-mediated current was recorded at different external concentrations of Na(+), Cl(-), or GABA. The shifts in V rev for a tenfold change in the external Na(+), Cl(-), and GABA concentration were 84 ± 4, 30 ± 1, and 29 ± 1 mV, respectively. To determine the net charge translocated per Na(+), Cl(-), and GABA, we measured substrate fluxes under voltage clamp in cells expressing GAT1 or GAT3. Charge flux to substrate flux ratios were 0.7 ± 0.1 charge/Na(+), 2.0 ± 0.2 charges/Cl(-), and 2.1 ± 0.1 charges/GABA. Altogether, our results strongly suggest a 3 Na(+):1 Cl(-):1 GABA coupling stoichiometry for the GABA transporters. The revised stoichiometry has important implications for understanding the contribution of GATs to GABAergic signaling in health and disease.
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Registered trials
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