Epithelial sodium channel (ENaC) in GtoPdb v.2021.2
Israel Hanukoglu2021, IUPHAR/BPS Guide to Pharmacology CITE
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The epithelial sodium channels (ENaC) are located on the apical membrane of epithelial cells in the kidney tubules, lung, respiratory tract, male and female reproductive tracts, sweat and salivary glands, placenta, colon, and some other organs [9, 13, 22, 21, 42]. In these epithelia, Na+ ions flow from the extracellular fluid into the cytoplasm of epithelial cells via ENaC. The Na+ ions are then pumped out of the cytoplasm into the interstitial fluid by the Na+/K+ ATPase located on the basolateral membrane [36]. As Na+ is one of the major electrolytes in the extracellular fluid (ECF), osmolarity change initiated by the Na+ flow is accompanied by a flow of water accompanying Na+ ions [6]. Thus, ENaC has a central role in regulating ECF volume and blood pressure, primarily via its function in the kidney [37]. The expression of ENaC subunits, hence its activity, is regulated by the renin-angiotensin-aldosterone system, and other factors involved in electrolyte homeostasis [37, 30]. In ...
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A major regulator of blood pressure and volume homeostasis in the kidney is the epithelial sodium channel (ENaC). ENaC is composed of alpha(α)/beta(β)/gamma(γ) or delta(δ)/beta(β)/gamma(γ) subunits. The δ subunit is functional in the guinea pig, but not in routinely used experimental rodent models including rat or mouse, and thus remains the least understood of the four subunits. While the δ subunit is poorly expressed in the human kidney, we recently found that its gene variants are associated with blood pressure and kidney function. The δ subunit is expressed in the human vasculature where it may influence vascular function. Moreover, we recently found that the δ subunit is also expressed human antigen presenting cells (APCs). Our studies indicate that extracellular Na+ enters APCs via ENaC leading to inflammation and salt-induced hypertension. In this review, we highlight recent findings on the role of extra-renal ENaC in inflammation, vascular dysfunction, and blood pressure mod...
IUPHAR/BPS Guide to Pharmacology CITE
https://doi.org/10.2218/gtopdb/F122/2021.2
Epithelial sodium channel (ENaC) in GtoPdb v.2021.2
Israel Hanukoglu1
1. Ariel University, Israel
Abstract
The epithelial sodium channels (ENaC) are located on the apical membrane of epithelial cells in the
kidney tubules, lung, respiratory tract, male and female reproductive tracts, sweat and salivary
glands, placenta, colon, and some other organs [9, 13, 22, 21, 42]. In these epithelia, Na+ ions flow
from the extracellular fluid into the cytoplasm of epithelial cells via ENaC. The Na+ ions are then
pumped out of the cytoplasm into the interstitial fluid by the Na+/K+ ATPase located on the
basolateral membrane [36]. As Na+ is one of the major electrolytes in the extracellular fluid (ECF),
osmolarity change initiated by the Na+ flow is accompanied by a flow of water accompanying Na+
ions [6]. Thus, ENaC has a central role in regulating ECF volume and blood pressure, primarily via its
function in the kidney [37]. The expression of ENaC subunits, hence its activity, is regulated by the
renin-angiotensin-aldosterone system, and other factors involved in electrolyte homeostasis [37, 30].
In the respiratory tract and female reproductive tract, large segments of the epithelia are composed
of multi-ciliated cells. In these cells, ENaC is located along the entire length of the cilia that cover
the cell surface [15]. Cilial location greatly increases ENaC density per cell surface and allows ENaC
to serve as a sensitive regulator of osmolarity of the periciliary fluid throughout the whole depth of
the fluid bathing the cilia [15]. In contrast to ENaC, CFTR (ion transporter defective in cystic
fibrosis) is located on non-cilial cell-surface [15]. In the vas deferens segment of the male
reproductive tract, the luminal surface is covered by microvilli and stereocilia projections with
backbones composed of actin filament bundles [42]. In these cells, both ENaC and the water channel
aquaporin AQP9 are localized on these projections and also in the basal and smooth muscle layers
[42]. Thus, ENaC function is also essential for the clearance of respiratory airways, transport of germ
cells, fertilization, implantation, and cell migration [15, 22].
Contents
This is a citation summary for Epithelial sodium channel (ENaC) in the Guide to Pharmacology
database (GtoPdb). It exists purely as an adjunct to the database to facilitate the recognition of
citations to and from the database by citation analyzers. Readers will almost certainly want to visit
the relevant sections of the database which are given here under database links.
GtoPdb is an expert-driven guide to pharmacological targets and the substances that act on them.
GtoPdb is a reference work which is most usefully represented as an on-line database. As in any
publication this work should be appropriately cited, and the papers it cites should also be recognized.
This document provides a citation for the relevant parts of the database, and also provides a
reference list for the research cited by those parts. For further details see [7].
Please note that the database version for the citations given in GtoPdb are to the most recent
preceding version in which the family or its subfamilies and targets were substantially changed. The
links below are to the current version. If you need to consult the cited version, rather than the most
recent version, please contact the GtoPdb curators.
Database links
Epithelial sodium channel (ENaC)
https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=122
Introduction to Epithelial sodium channel (ENaC)
https://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=122
Channels and Subunits
Complexes
ENaCαβγ
https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=742
Subunits
ENaC α
https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=738
ENaC β
https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=739
ENaC γ
https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=741
ENaC δ
https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=740
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