Sodium–bicarbonate cotransporter NBCn1/Slc4a7 inhibits NH 4 Cl‐mediated inward current in Xenopus oocytes

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 m m ) 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 m m 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.