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Annual Review of Physiology

Volume 87, 2025

Epithelial Na+ Channels, Immune Cells, and Salt

  • Annet Kirabo1, Sepiso K. Masenga2 and Thomas R. Kleyman3,4
  • 1Division of Clinical Pharmacology, Department of Medicine, Department of Molecular Physiology and Biophysics, Vanderbilt Center for Immunobiology, Vanderbilt Institute for Infection, Immunology and Inflammation and Vanderbilt Institute for Global Health, Vanderbilt University Medical Center, Vanderbilt University, Nashville, Tennessee, USA 2HAND Research Group, School of Medicine and Health Sciences, Mulungushi University, Livingstone Campus, Livingstone, Zambia 3Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; email: [email protected] 4Department of Cell Biology and Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  • Vol. 87:381-395 (Volume publication date February 2025)
  • First published as a Review in Advance on November 12, 2024
  • Copyright © 2025 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

Epithelial Na+ channels (ENaCs) are known to affect blood pressure through their role in transporting Na+ in the distal nephron of the kidney. While expressed in other epithelial tissues, there is growing evidence that ENaCs are also expressed in nonepithelial tissues where their activity influences blood pressure. This review provides an overview of ENaCs and key mechanisms that regulate channel activity. The role of ENaCs in antigen-presenting dendritic cells is discussed, where ENaC-dependent sensing of increases in the extracellular Na+ concentration leads to activation of a signaling cascade, T cell activation with the release of proinflammatory cytokines, and an increase in blood pressure. The potential contribution of this pathway to human hypertension is discussed.

Keyword(s): aldosterone, dendritic cells, ENaC, hypertension, protease, sodium
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Epithelial Na+ Channels, Immune Cells, and Salt
Annual Review of Physiology 87, 381 (2025); https://doi.org/10.1146/annurev-physiol-022724-105050
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