title: The sodium-bicarbonate cotransporter NBCe1 supports glutamine efflux via SNAT3 (SLC38A3) co-expressed in Xenopus oocytes.
abstract: The glutamine transporter SNAT3 contributes to the glutamine fluxes in liver, kidney, and brain. We heterologously co-expressed SNAT3 with the electrogenic sodium-bicarbonate cotransporter NBCe1 in Xenopus laevis oocytes and measured cytosolic pH and membrane current in voltage clamp. Because of the increased buffer capacity contributed by the NBCe1 (Becker and Deitmer in J Biol Chem 279:28057-28062, 2004), we hypothesized that this may enhance the proton-coupled glutamine transport via SNAT3 in the presence of CO2/HCO3-. Addition and removal of glutamine activated not only SNAT3 but also NBCe1, as indicated by the increased membrane current. The NBCe1 current during glutamine removal was more than 50% larger than during glutamine addition, suggesting that NBCe1 enhances glutamine efflux rather than glutamine uptake. This was confirmed by radio-labeled glutamine flux measurements; influx of glutamine was significantly decreased, whereas efflux of glutamine was increased when SNAT3 was co-expressed with NBCe1. A model is presented that attempts to explain the role of intracellular pH, bicarbonate transport, and buffering capacity mediated by NBCe1 for uptake and efflux of glutamine via SNAT3.
authors.affiliation: Abteilung für Allgemeine Zoologie, FB Biologie, TU Kaiserslautern, P.O. Box 3049, 67653 Kaiserslautern, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Wendel
authors.forename: Holger M
authors.initials: HM
authors.lastname: Becker
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Deitmer
mesh_terms: D000136:Acid-Base Equilibrium / Q000502:physiology; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D002021:Buffers; D002250:Carbon Radioisotopes; D003600:Cytosol / Q000378:metabolism; D005973:Glutamine / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials / Q000502:physiology; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D011522:Protons; D051381:Rats; D012964:Sodium / Q000378:metabolism; D027982:Sodium-Bicarbonate Symporters / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D014982:Xenopus laevis
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D001639:Bicarbonates; D002021:Buffers; D002250:Carbon Radioisotopes; D011522:Protons; C422004:Slc4a4 protein, rat; D027982:Sodium-Bicarbonate Symporters; C403222:system N protein 1; D005973:Glutamine; D012964:Sodium