Characterization of Human SLC4A10 as an Electroneutral Na/HCO sub(3) Cotransporter (NBCn2) with Cl super(-) Self-exchange Activity

• Published in: The Journal of biological chemistry 2008-05, Vol.283 (19), p.12777-12788
• Main Authors: Parker, Mark D, Musa-Aziz, Raif, Rojas, Jose D, Choi, Inyeong, Daly, Christopher M, Boron, Walter F
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X

The SLC4A10 gene product, commonly known as NCBE, is highly expressed in rodent brain and has been characterized by others as a Na super(+)-driven Cl-HCO sub(3) exchanger. However, some of the earlier data are not consistent with Na super(+)-driven Cl-HCO sub(3) 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 super(+)-dependent transport of [Formula: see text]. For the first time, we demonstrated that this transport process is electroneutral. Using Cl super(-)-sensitive microelectrodes positioned at the oocyte surface, we found that, unlike both human and squid Na super(+)-driven Cl-HCO sub(3) exchangers, human NCBE does not normally couple the net influx of [Formula: see text] to a net efflux of Cl super(-). Moreover we found that that the super(36)Cl efflux from NCBE-expressing oocytes, interpreted by others to be coupled to the influx of Na super(+) and [Formula: see text], actually represents a [Formula: see text]-stimulated Cl super(-) self-exchange not coupled to either Na super(+) or net [Formula: see text] transport. We propose to rename NCBE as the second electroneutral Na/HCO sub(3) cotransporter, NBCn2.