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J Gen Physiol 2006 May 01;1275:511-24. doi: 10.1085/jgp.200509392.
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Coupling modes and stoichiometry of Cl-/HCO3- exchange by slc26a3 and slc26a6.

Shcheynikov N , Wang Y , Park M , Ko SB , Dorwart M , Naruse S , Thomas PJ , Muallem S .

The SLC26 transporters are a family of mostly luminal Cl- and HCO3- transporters. The transport mechanism and the Cl-/HCO3- stoichiometry are not known for any member of the family. To address these questions, we simultaneously measured the HCO3- and Cl- fluxes and the current or membrane potential of slc26a3 and slc26a6 expressed in Xenopus laevis oocytes and the current of the transporters expressed in human embryonic kidney 293 cells. slc26a3 mediates a coupled 2Cl-/1HCO3- exchanger. The membrane potential modulated the apparent affinity for extracellular Cl- of Cl-/HCO3- exchange by slc26a3. Interestingly, the replacement of Cl- with NO3- or SCN- uncoupled the transport, with large NO3- and SCN- currents and low HCO3- transport. An apparent uncoupled current was also developed during the incubation of slc26a3-expressing oocytes in HCO3--buffered Cl--free media. These findings were used to develop a turnover cycle for Cl- and HCO3- transport by slc26a3. Cl- and HCO3- flux measurements revealed that slc26a6 mediates a 1Cl-/2HCO3- exchange. Accordingly, holding the membrane potential at 40 and -100 mV accelerated and inhibited, respectively, Cl--mediated HCO3- influx, and holding the membrane potential at -100 mV increased HCO3--mediated Cl- influx. These findings indicate that slc26a6 functions as a coupled 1Cl-/2HCO3- exchanger. The significance of isoform-specific Cl- and HCO3- transport stoichiometry by slc26a3 and slc26a6 is discussed in the context of diseases of epithelial Cl- absorption and HCO3- secretion.

PubMed ID: 16606687
PMC ID: PMC2151520
Article link: J Gen Physiol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: nbl1 slc26a3.1 slc26a3.2 slc26a6 slc4a1 sri
GO keywords: ion transport

Disease Ontology terms: congenital secretory chloride diarrhea 1 [+]

Article Images: [+] show captions
References [+] :
Accardi, Secondary active transport mediated by a prokaryotic homologue of ClC Cl- channels. 2004, Pubmed