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The anion exchanger PAT-1 (Slc26a6) does not participate in oxalate or chloride transport by mouse large intestine

  • Ion channels, receptors and transporters
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Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

The membrane-bound transport proteins responsible for oxalate secretion across the large intestine remain unidentified. The apical chloride/bicarbonate (Cl−/HCO3−) exchanger encoded by Slc26a6, known as PAT-1 (putative anion transporter 1), is a potential candidate. In the small intestine, PAT-1 makes a major contribution to oxalate secretion but whether this role extends into the large intestine has not been directly tested. Using the PAT-1 knockout (KO) mouse, we compared the unidirectional absorptive (\( {J}_{ms}^{ion} \)) and secretory (\( {J}_{sm}^{ion} \)) flux of oxalate and Cl− across cecum, proximal colon, and distal colon from wild-type (WT) and KO mice in vitro. We also utilized the non-specific inhibitor DIDS (4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid) to confirm a role for PAT-1 in WT large intestine and (in KO tissues) highlight any other apical anion exchangers involved. Under symmetrical, short-circuit conditions the cecum and proximal colon did not transport oxalate on a net basis, whereas the distal colon supported net secretion. We found no evidence for the participation of PAT-1, or indeed any other DIDS-sensitive transport mechanism, in oxalate or Cl− by the large intestine. Most unexpectedly, mucosal DIDS concurrently stimulated \( {J}_{ms}^{Ox} \) and \( {J}_{sm}^{Ox} \) by 25–68% across each segment without impacting net transport. For the colon, these changes were directly proportional to increased transepithelial conductance suggesting this response was the result of bidirectional paracellular flux. In conclusion, PAT-1 does not contribute to oxalate or Cl− transport by the large intestine, and we urge caution when using DIDS with mouse colonic epithelium.

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Acknowledgments

The authors wish to thank Carolyn Avila-Duran, Maureen Mohan, and Morgan Parker for animal husbandry.

Funding

This work was supported by National Institutes of Health grants DK-108755 and DK-088892 to M. Hatch. J. Whittamore was also supported by a research grant from the Oxalosis & Hyperoxaluria Foundation.

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  1. Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, PO Box 100275, 1600 SW Archer Rd, Gainesville, FL, 32610, USA

    Jonathan M. Whittamore & Marguerite Hatch

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  1. Jonathan M. Whittamore
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  2. Marguerite Hatch
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Contributions

J.W. and M.H. conceived and designed the study; J.W. performed the research; J.W. and M.H. analyzed the data; J.W. wrote the paper.

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Correspondence to Jonathan M. Whittamore.

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All animal experimentation was approved by the University of Florida Institutional Animal Care and Use Committee (IACUC) and conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

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Whittamore, J.M., Hatch, M. The anion exchanger PAT-1 (Slc26a6) does not participate in oxalate or chloride transport by mouse large intestine. Pflugers Arch - Eur J Physiol 473, 95–106 (2021). https://doi.org/10.1007/s00424-020-02495-x

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  • DOI: https://doi.org/10.1007/s00424-020-02495-x

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