Molecular and functional characterization of the electroneutral Na/HCO3 cotransporter NBCn1 in rat hippocampal neurons

J Biol Chem. 2005 May 6;280(18):17823-30. doi: 10.1074/jbc.M408646200. Epub 2005 Feb 17.


We examined molecular and electrophysiological properties of the electroneutral sodium/bicarbonate cotransporter (NBCn1) that is present in rat hippocampal neurons. By PCR, a deletion variant (NBCn1-E) that lacks 123 amino acids in the cytoplasmic N-terminal domain was found in adult neurons. The previously characterized NBCn1-B, which does not have the deletion, was detected in embryonic neurons. In Xenopus oocytes, NBCn1-E raised the intracellular pH in the presence of HCO(3) without significantly affecting the membrane potential. Despite this electroneutral cotransport activity, the transporter mediated a steady-state current that positively shifted the resting potential by almost 30 mV. The mean reversal potential of the steady-state current was -21.2 mV, close to the resting potential of -21.4 mV. The reversal potential shifted 26 mV in response to a 10-fold increase of external Na(+) for concentrations above 10 mm. The current activity mediated by the transporter was unaffected by K(+), Mg(2+), Ca(2+), or Cl(-). Stable expression of NBCn1-E in human embryonic kidney cells also evoked an inward current that shifted the resting potentials more positive compared with the sham-transfected controls. In primary cultures of embryonic hippocampal neurons, the NBCn1 protein was localized in somatodendrites and synapses. NBCn1 protein was partially colocalized with the postsynaptic density protein PSD-95. Single-cell PCR showed that NBCn1 mRNA expression was present in both gamma-aminobutyric acid (GABA)ergic and non-GABAergic neurons. We propose that NBCn1 in hippocampal neurons may affect neuronal activity by regulating local pH as well as steady-state inward currents at synapses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Female
  • Hippocampus / metabolism*
  • Humans
  • Hydrogen-Ion Concentration
  • Neurons / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Bicarbonate Symporters / chemistry*
  • Sodium-Bicarbonate Symporters / metabolism*
  • Sodium-Bicarbonate Symporters / physiology*
  • Synapses / metabolism
  • Xenopus


  • SLC4A4 protein, human
  • Slc4a4 protein, rat
  • Sodium-Bicarbonate Symporters