Characterization of human SLC4A10 as an electroneutral Na/HCO3 cotransporter (NBCn2) with Cl- self-exchange activity

Mark D. Parker, Raif Musa-Aziz, Jose Rojas, Inyeong Choi, Christopher M. Daly, Walter F. Boron

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

The SLC4A10 gene product, commonly known as NCBE, is highly expressed in rodent brain and has been characterized by others as a Na+-driven Cl-HCO3 exchanger. However, some of the earlier data are not consistent with Na+-driven Cl-HCO3 exchange activity. In the present study, northern blot analysis showed that, also in humans, NCBE transcripts are predominantly expressed in brain. In some human NCBE transcripts, splice cassettes A and/or B, originally reported in rats and mice, are spliced out. In brain cDNA, we found evidence of a unique partial splice of cassette B that is predicted to produce an NCBE protein with a novel C terminus containing a protein kinase C phosphorylation site. We used pH-sensitive microelectrodes to study the molecular physiology of human NCBE expressed in Xenopus oocytes. In agreement with others we found that NCBE mediates the 4,4′-diisothiocyanato-stilbene-2,2′-disulfonic acid-sensitive, Na+-dependent transport of HCO3 -. For the first time, we demonstrated that this transport process is electroneutral. Using Cl--sensitive microelectrodes positioned at the oocyte surface, we found that, unlike both human and squid Na+-driven Cl-HCO3 exchangers, human NCBE does not normally couple the net influx of HCO 3 - to a net efflux of Cl-. Moreover we found that that the 36Cl efflux from NCBE-expressing oocytes, interpreted by others to be coupled to the influx of Na+ and HCO3 -, actually represents a CO2/HCO3 --stimulated Cl- self-exchange not coupled to either Na+ or net HCO3 - transport. We propose to rename NCBE as the second electroneutral Na/HCO3 cotransporter, NBCn2.

Original languageEnglish (US)
Pages (from-to)12777-12788
Number of pages12
JournalJournal of Biological Chemistry
Volume283
Issue number19
DOIs
StatePublished - May 9 2008

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ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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