Publications

• Coupling modes and stoichiometry of Cl-/HCO3- exchange by slc26a3 and slc26a6.

  Shcheynikov N., Wang Y., Park M., Ko S.B., Dorwart M., Naruse S., Thomas P.J., 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 o ... >> More

  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. << Less

  J. Gen. Physiol. 127:511-524(2006) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• A molecular mechanism for aberrant CFTR-dependent HCO(3)(-) transport in cystic fibrosis.

  Ko S.B., Shcheynikov N., Choi J.Y., Luo X., Ishibashi K., Thomas P.J., Kim J.Y., Kim K.H., Lee M.G., Naruse S., Muallem S.

  Aberrant HCO(3)(-) transport is a hallmark of cystic fibrosis (CF) and is associated with aberrant Cl(-)-dependent HCO(3)(-) transport by the cystic fibrosis transmembrane conductance regulator (CFTR). We show here that HCO(3)(-) current by CFTR cannot account for CFTR-activated HCO(3)(-) transpor ... >> More

  Aberrant HCO(3)(-) transport is a hallmark of cystic fibrosis (CF) and is associated with aberrant Cl(-)-dependent HCO(3)(-) transport by the cystic fibrosis transmembrane conductance regulator (CFTR). We show here that HCO(3)(-) current by CFTR cannot account for CFTR-activated HCO(3)(-) transport and that CFTR does not activate AE1-AE4. In contrast, CFTR markedly activates Cl(-) and OH(-)/HCO(3)(-) transport by members of the SLC26 family DRA, SLC26A6 and pendrin. Most notably, the SLC26s are electrogenic transporters with isoform-specific stoichiometries. DRA activity occurred at a Cl(-)/HCO(3)(-) ratio > or =2. SLC26A6 activity is voltage regulated and occurred at HCO(3)(-)/Cl(-) > or =2. The physiological significance of these findings is demonstrated by interaction of CFTR and DRA in the mouse pancreas and an altered activation of DRA by the R117H and G551D mutants of CFTR. These findings provide a molecular mechanism for epithelial HCO(3)(-) transport (one SLC26 transporter-electrogenic transport; two SLC26 transporters with opposite stoichiometry in the same membrane domain-electroneutral transport), the CF-associated aberrant HCO(3)(-) transport, and reveal a new function of CFTR with clinical implications for CF and congenital chloride diarrhea. << Less

  EMBO J 21:5662-5672(2002) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.