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Slc26a9—Anion Exchanger, Channel and Na+ Transporter

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Abstract

The SLC26 gene family encodes anion transporters with diverse functional attributes: (a) anion exchanger, (b) anion sensor, and (c) anion conductance (likely channel). We have cloned and studied Slc26a9, a paralogue expressed mostly in lung and stomach. Immunohistochemistry shows that Slc26a9 is present at apical and intracellular membranes of lung and stomach epithelia. Using expression in Xenopus laevis oocytes and ion-sensitive microelectrodes, we discovered that Slc26a9 has a novel function not found in any other Slc26 proteins: cation coupling. Intracellular pH and voltage measurements show that Slc26a9 is a nCl−-HCO −3 exchanger, suggesting roles in gastric HCl secretion or pulmonary HCO −3 secretion; Na+ electrodes and uptakes reveal that Slc26a9 has a cation dependence. Single-channel measurements indicate that Slc26a9 displays discrete open and closed states. These experiments show that Slc26a9 has three discrete physiological modes: nCl−-HCO −3 exchanger, Cl− channel, and Na+-anion cotransporter. Thus, the Slc26a9 transporter channel is uniquely suited for dynamic and tissue-specific physiology or regulation in epithelial tissues.

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Acknowledgments

We thank N. Angle, G. Babcock, L. Song, Q. Xie, R. Welch, and M. Sanders for excellent technical support. We thank Dr. S. Muallem for the Slc26a7 cDNA. We also thank Drs. S. W. Jones and C. Objero-Paz for discussions and initial patch experiments. This work was supported by NIH Grants DK056218, DK060845, and EY017732 (M.F.R.); DK038226, DK070756, and DK57708 (D.B.M.); and F32-DK65482 (V·B.). Other funding includes an Advanced Career Development Award from the Veterans Administration (DBM); the Wadsworth Foundation & American Heart Association (AHA; C.R.S.); a postdoctoral fellowship from the AHA (M.-H·C. and K.Z.); and the Cystic Fibrosis Foundation (ROMERO-06GO and SINDIC-06F0).

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Authors and Affiliations

  1. Physiology & Biophysics, Case Western Reserve University, Cleveland, OH, 44106, USA

    Min-Hwang Chang, Consuelo Plata, Aleksandra Sinđić, Caroline R. Sussman & Michael F. Romero

  2. Department of Physiology & Biomedical Engineering, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA

    Min-Hwang Chang, Aleksandra Sinđić, Caroline R. Sussman & Michael F. Romero

  3. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico, 14000, México

    Consuelo Plata

  4. Renal Division, Brigham & Women’s Hospital, Boston, MA, 02115, USA

    Kambiz Zandi-Nejad, Adriana Mercado, Vadjista Broumand & David B. Mount

  5. Physiology, School of Medicine, Croatian Institute for Brain Research, University of Zagreb, Zagreb, Croatia

    Aleksandra Sinđić

  6. NHLBI, NIH, Bethesda, MD, 20892, USA

    Viswanathan Raghuram

  7. Renal Division, VA Boston Healthcare System, West Roxbury, MA, 02132, USA

    David B. Mount

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  1. Min-Hwang Chang
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  2. Consuelo Plata
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  3. Kambiz Zandi-Nejad
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  7. Vadjista Broumand
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  8. Viswanathan Raghuram
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  9. David B. Mount
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  10. Michael F. Romero
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Correspondence to Michael F. Romero.

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Min-Hwang Chang, Consuelo Plata, and Kambiz Zandi-Nejad have contributed equally to this work.

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Chang, MH., Plata, C., Zandi-Nejad, K. et al. Slc26a9—Anion Exchanger, Channel and Na+ Transporter. J Membrane Biol 228, 125–140 (2009). https://doi.org/10.1007/s00232-009-9165-5

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