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Luminal Na+/H+ exchange in the proximal tubule

  • Transport Physiology
  • Published:
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Abstract

The proximal tubule is critical for whole-organism volume and acid–base homeostasis by reabsorbing filtered water, NaCl, bicarbonate, and citrate, as well as by excreting acid in the form of hydrogen and ammonium ions and producing new bicarbonate in the process. Filtered organic solutes such as amino acids, oligopeptides, and proteins are also retrieved by the proximal tubule. Luminal membrane Na+/H+ exchangers either directly mediate or indirectly contribute to each of these processes. Na+/H+ exchangers are a family of secondary active transporters with diverse tissue and subcellular distributions. Two isoforms, NHE3 and NHE8, are expressed at the luminal membrane of the proximal tubule. NHE3 is the prevalent isoform in adults, is the most extensively studied, and is tightly regulated by a large number of agonists and physiological conditions acting via partially defined molecular mechanisms. Comparatively little is known about NHE8, which is highly expressed at the lumen of the neonatal proximal tubule and is mostly intracellular in adults. This article discusses the physiology of proximal Na+/H+ exchange, the multiple mechanisms of NHE3 regulation, and the reciprocal relationship between NHE3 and NHE8 at the lumen of the proximal tubule.

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Acknowledgements

We thank Dr. Michel Baum for helpful and insightful discussions. The authors were supported by the National Institutes of Health (R01-DK-48482 and P01-DK-020543 to O.W.M.), the Simmons Family Foundation (O.W.M.), the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research (fellowship grant to I.A.B.), and by the American Society of Nephrology (Carl W. Gottschalk Research Scholar Award to I.A.B.).

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  1. Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8856, USA

    I. Alexandru Bobulescu & Orson W. Moe

  2. Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8856, USA

    I. Alexandru Bobulescu & Orson W. Moe

  3. Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8856, USA

    Orson W. Moe

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Bobulescu, I.A., Moe, O.W. Luminal Na+/H+ exchange in the proximal tubule. Pflugers Arch - Eur J Physiol 458, 5–21 (2009). https://doi.org/10.1007/s00424-008-0595-1

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