ArticleThe Journal of membrane biology2005
Novel properties of a mouse gamma-aminobutyric acid transporter (GAT4).
Article in The Journal of membrane biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Amino Acid Transporter SLC6A14 (ATBFrontiers in cell and developmental biology · 2020Review
- Di- and tripeptide transport in vertebrates: the contribution of teleost fish models.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2017Review
- Evidence for a Revised Ion/Substrate Coupling Stoichiometry of GABA Transporters.The Journal of membrane biology · 2015Article
- Glutamate as a neurotransmitter in the healthy brain.Journal of neural transmission (Vienna, Austria : 1996) · 2014Review
- Teleost fish models in membrane transport research: the PEPT1(SLC15A1) H+-oligopeptide transporter as a case study.The Journal of physiology · 2014Review
- The betaine/GABA transporter and betaine: roles in brain, kidney, and liver.Frontiers in physiology · 2014Review
- Cl⁻ homeodynamics in gap junction-coupled astrocytic networks on activation of GABAergic synapses.The Journal of physiology · 2013Article
- Rate and regulation of copper transport by human copper transporter 1 (hCTR1).The Journal of biological chemistry · 2013Article
- Protein cold adaptation strategy via a unique seven-amino acid domain in the icefish (Chionodraco hamatus) PEPT1 transporter.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- GABA and Glutamate Transporters in Brain.Frontiers in endocrinology · 2013Review
- Functional consequences of sulfhydryl modification of the γ-aminobutyric acid transporter 1 at a single solvent-exposed cysteine residue.The Journal of membrane biology · 2012Article
- The solute carrier 6 family of transporters.British journal of pharmacology · 2012Review
- Functional expression of γ-amino butyric acid transporter 2 in human and guinea pig airway epithelium and smooth muscle.American journal of respiratory cell and molecular biology · 2011Article
- Localization and Function of GABA Transporters GAT-1 and GAT-3 in the Basal Ganglia.Frontiers in systems neuroscience · 2011Article
- Pharmacological analysis of the activation and receptor properties of the tonic GABA(C)R current in retinal bipolar cell terminals.PloS one · 2011Article
- The actual ionic nature of the leak current through the Na+/glucose cotransporter SGLT1.Biophysical journal · 2010Article
- GATMD: γ-aminobutyric acid transporter mutagenesis database.Database : the journal of biological databases and curation · 2010Article
- Inhibitors of the gamma-aminobutyric acid transporter 1 (GAT1) do not reveal a channel mode of conduction.Neurochemistry international · 2009Article
- Turnover rate of the gamma-aminobutyric acid transporter GAT1.The Journal of membrane biology · 2007Article
- Assessing the ability of sequence-based methods to provide functional insight within membrane integral proteins: a case study analyzing the neurotransmitter/Na+ symporter family.BMC bioinformatics · 2007Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
We expressed the mouse gamma-aminobutyric acid (GABA) transporter GAT4 (homologous to rat/ human GAT-3) in Xenopus laevis oocytes and examined its functional and pharmacological properties by using electrophysiological and tracer uptake methods. In the coupled mode of transport (Na+/ Cl-/GABA cotransport), there was tight coupling between charge flux and GABA flux across the plasma membrane (2 charges/GABA). Transport was highly temperature-dependent with a temperature coefficient (Q10) of 4.3. The GAT4 turnover rate (1.5 s(-l); -50 mV, 21 degrees C) and temperature dependence suggest physiological turnover rates of 15-20 s(-1). No uncoupled current was observed in the presence of Na+. In the absence of external Na+, GAT4 exhibited two distinct uncoupled currents. (i) A Cl- leak current (ICl(leak)) was observed when Na+ was replaced with choline or tetraethylammonium. The reversal potential of (ICl(leak)) followed the Cl- Nernst potential. (ii) A Li+ leak current (ILi(leak)) was observed when Na+ was replaced with Li+. Both leak currents were inhibited by Na+, and both were temperature-independent (Q10 approximately 1). The two leak modes appeared not to coexist, as Li+ inhibited (ICl(leak)). The results suggest the existence of cation- and anion-selective channel-like pathways in GAT4. Flufenamic acid inhibited GAT4 Na+/Cl-/GABA cotransport, ILi(leak), and ICl(leak), (Ki approximately 30 microM), and the voltage-induced presteady-state charge movements (Ki approximately 440 microM). Flufenamic acid exhibited little or no selectivity for GAT1, GAT2, or GAT3. Sodium and GABA concentration jicroumps revealed that slow Na+ binding to the transporter is followed by rapid GABA-induced translocation of the ligands across the plasma membrane. Thus, Na+ binding and associated conformational changes constitute the rate-limiting steps in the transport cycle.
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