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Coupling Modes and Stoichiometry of Cl(−)/HCO(3) (−) Exchange by slc26a3 and slc26a6
The SLC26 transporters are a family of mostly luminal Cl(−) and HCO(3) (−) transporters. The transport mechanism and the Cl(−)/HCO(3) (−) stoichiometry are not known for any member of the family. To address these questions, we simultaneously measured the HCO(3) (−) and Cl(−) fluxes and the current o...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151520/ https://www.ncbi.nlm.nih.gov/pubmed/16606687 http://dx.doi.org/10.1085/jgp.200509392 |
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author | Shcheynikov, Nikolay Wang, Youxue Park, Meeyoung Ko, Shigeru B.H. Dorwart, Michael Naruse, Satoru Thomas, Philip J. Muallem, Shmuel |
author_facet | Shcheynikov, Nikolay Wang, Youxue Park, Meeyoung Ko, Shigeru B.H. Dorwart, Michael Naruse, Satoru Thomas, Philip J. Muallem, Shmuel |
author_sort | Shcheynikov, Nikolay |
collection | PubMed |
description | The SLC26 transporters are a family of mostly luminal Cl(−) and HCO(3) (−) transporters. The transport mechanism and the Cl(−)/HCO(3) (−) stoichiometry are not known for any member of the family. To address these questions, we simultaneously measured the HCO(3) (−) 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(−)/1HCO(3) (−) exchanger. The membrane potential modulated the apparent affinity for extracellular Cl(−) of Cl(−)/HCO(3) (−) exchange by slc26a3. Interestingly, the replacement of Cl(−) with NO(3) (−) or SCN(−) uncoupled the transport, with large NO(3) (−) and SCN(−) currents and low HCO(3) (−) transport. An apparent uncoupled current was also developed during the incubation of slc26a3-expressing oocytes in HCO(3) (−)-buffered Cl(−)-free media. These findings were used to develop a turnover cycle for Cl(−) and HCO(3) (−) transport by slc26a3. Cl(−) and HCO(3) (−) flux measurements revealed that slc26a6 mediates a 1Cl(−)/2HCO(3) (−) exchange. Accordingly, holding the membrane potential at 40 and −100 mV accelerated and inhibited, respectively, Cl(−)-mediated HCO(3) (−) influx, and holding the membrane potential at −100 mV increased HCO(3) (−)-mediated Cl(−) influx. These findings indicate that slc26a6 functions as a coupled 1Cl(−)/2HCO(3) (−) exchanger. The significance of isoform-specific Cl(−) and HCO(3) (−) transport stoichiometry by slc26a3 and slc26a6 is discussed in the context of diseases of epithelial Cl(−) absorption and HCO(3) (−) secretion. |
format | Text |
id | pubmed-2151520 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21515202008-01-17 Coupling Modes and Stoichiometry of Cl(−)/HCO(3) (−) Exchange by slc26a3 and slc26a6 Shcheynikov, Nikolay Wang, Youxue Park, Meeyoung Ko, Shigeru B.H. Dorwart, Michael Naruse, Satoru Thomas, Philip J. Muallem, Shmuel J Gen Physiol Articles The SLC26 transporters are a family of mostly luminal Cl(−) and HCO(3) (−) transporters. The transport mechanism and the Cl(−)/HCO(3) (−) stoichiometry are not known for any member of the family. To address these questions, we simultaneously measured the HCO(3) (−) 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(−)/1HCO(3) (−) exchanger. The membrane potential modulated the apparent affinity for extracellular Cl(−) of Cl(−)/HCO(3) (−) exchange by slc26a3. Interestingly, the replacement of Cl(−) with NO(3) (−) or SCN(−) uncoupled the transport, with large NO(3) (−) and SCN(−) currents and low HCO(3) (−) transport. An apparent uncoupled current was also developed during the incubation of slc26a3-expressing oocytes in HCO(3) (−)-buffered Cl(−)-free media. These findings were used to develop a turnover cycle for Cl(−) and HCO(3) (−) transport by slc26a3. Cl(−) and HCO(3) (−) flux measurements revealed that slc26a6 mediates a 1Cl(−)/2HCO(3) (−) exchange. Accordingly, holding the membrane potential at 40 and −100 mV accelerated and inhibited, respectively, Cl(−)-mediated HCO(3) (−) influx, and holding the membrane potential at −100 mV increased HCO(3) (−)-mediated Cl(−) influx. These findings indicate that slc26a6 functions as a coupled 1Cl(−)/2HCO(3) (−) exchanger. The significance of isoform-specific Cl(−) and HCO(3) (−) transport stoichiometry by slc26a3 and slc26a6 is discussed in the context of diseases of epithelial Cl(−) absorption and HCO(3) (−) secretion. The Rockefeller University Press 2006-05 /pmc/articles/PMC2151520/ /pubmed/16606687 http://dx.doi.org/10.1085/jgp.200509392 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Shcheynikov, Nikolay Wang, Youxue Park, Meeyoung Ko, Shigeru B.H. Dorwart, Michael Naruse, Satoru Thomas, Philip J. Muallem, Shmuel Coupling Modes and Stoichiometry of Cl(−)/HCO(3) (−) Exchange by slc26a3 and slc26a6 |
title | Coupling Modes and Stoichiometry of Cl(−)/HCO(3)
(−) Exchange by slc26a3 and slc26a6 |
title_full | Coupling Modes and Stoichiometry of Cl(−)/HCO(3)
(−) Exchange by slc26a3 and slc26a6 |
title_fullStr | Coupling Modes and Stoichiometry of Cl(−)/HCO(3)
(−) Exchange by slc26a3 and slc26a6 |
title_full_unstemmed | Coupling Modes and Stoichiometry of Cl(−)/HCO(3)
(−) Exchange by slc26a3 and slc26a6 |
title_short | Coupling Modes and Stoichiometry of Cl(−)/HCO(3)
(−) Exchange by slc26a3 and slc26a6 |
title_sort | coupling modes and stoichiometry of cl(−)/hco(3)
(−) exchange by slc26a3 and slc26a6 |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151520/ https://www.ncbi.nlm.nih.gov/pubmed/16606687 http://dx.doi.org/10.1085/jgp.200509392 |
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