title: Sodium-bicarbonate cotransporter NBCn1/Slc4a7 inhibits NH4Cl-mediated inward current in Xenopus oocytes.
abstract: The electroneutral Na(+)-HCO(3)(-) cotransporter NBCn1 (SLC4A7) contributes to intracellular pH maintenance and transepithelial HCO(3)(-) movement. In this study, we expressed NBCn1 in Xenopus oocytes and examined the effect of NBCn1 on oocyte NH(4)(+) transport by analysing changes in membrane potential, current and intracellular pH mediated by NH(4)Cl. In the presence of HCO(3)(-)/CO(2), applying NH(4)Cl (20 mm) produced intracellular acidification of oocytes. The acidification was faster in oocytes expressing NBCn1 than in control oocytes injected with water; however, NH(4)Cl-mediated membrane depolarization was smaller in oocytes expressing NBCn1. In HCO(3)(-)/CO(2)-free solution, NH(4)Cl produced a smaller inward current in NBCn1-expressing oocytes (56% inhibition by 20 mm NH(4)Cl, measured at --60 mV), while minimally affecting intracellular acidification. The inhibition of the current by NBCn1 was unaffected when BaCl(2) replaced KCl. Current-voltage relationships showed a positive and nearly linear relationship between NH(4)Cl-mediated current and voltage, which was markedly reduced by NBCn1. Large basal currents (before NH(4)Cl exposure) were produced in NBCn1-expressing oocytes owing to the previously characterized channel-like activity of NBCn1. Inhibiting this channel-like activity by Na(+) removal abolished the inhibitory effect of NBCn1 on NH(4)Cl-mediated currents. The currents were progressively reduced over 72-120 h after NBCn1 cRNA injection, during which the channel-like activity was high. These results indicate that NBCn1 stimulates NH(4)(+) transport by its Na(+)-HCO(3)(-) cotransport activity, while reducing NH(4)(+) conductance by its channel-like activity.
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Soojung
authors.initials: S
authors.lastname: Lee
authors.forename: Inyeong
authors.initials: I
authors.lastname: Choi
mesh_terms: D000643:Ammonium Chloride / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D002245:Carbon Dioxide / Q000378:metabolism; D005260:Female; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D051381:Rats; D027982:Sodium-Bicarbonate Symporters / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D000644:Quaternary Ammonium Compounds; C498902:Slc4a7 protein, rat; D027982:Sodium-Bicarbonate Symporters; D000643:Ammonium Chloride; D002245:Carbon Dioxide