Role of the epithelial sodium channel (ENaC) in the development of salt‐sensitive hypertension

The purpose of this study was to examine the role of the serum- and glucocorticoid-induced kinase (SGK) in the activation of the epithelial sodium channel (ENaC) by aldosterone, arginine vasopressin (AVP), and insulin. We used a tetracycline-inducible system to control the expression of wild-type (SGK[Formula: see text]), constitutively active (S425D mutation; SGK[Formula: see text]), or inactive (K130M mutation; SGK[Formula: see text]) SGK in A6 cells independently of hormonal stimulation. The effect of SGK expression on ENaC activity was monitored by measuring transepithelial amiloride-sensitive short-circuit current ( I sc) of transfected A6 cell lines. Expression of SGK[Formula: see text] or SGK[Formula: see text] and aldosterone stimulation have additive effects on I sc. Although SGK could play some role in the aldosterone response, our results suggest that other mechanisms take place. SGK[Formula: see text] abrogates the responses to AVP and insulin; hence, in the signaling pathways of these hormones there is a shared step that is stimulated by SGK. Because AVP and insulin induce fusion of vesicles to the apical membrane, our results support the notion that SGK promotes incorporation of channels in the apical membrane.

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The role of Epithelial sodium channel (ENaC) in cell proliferation and tunneling nanotube (TnT) formation in benign mesothelial cells and malignant pleural mesothelioma (MPM) cells

10.1183/1393003.congress-2017.pa4300 ◽

2017 ◽

Author(s):

Rajesh Jagirdar ◽

Sotiris Zarogiannis ◽

Paschalis Adam Molyvdas ◽

Chrissa Hatzoglou ◽

Konstantinos Gourgoulianis

Keyword(s):

Cell Proliferation ◽

Sodium Channel ◽

Malignant Pleural Mesothelioma ◽

Epithelial Sodium Channel ◽

Mesothelial Cells ◽

Pleural Mesothelioma ◽

Tunneling Nanotube ◽

Epithelial Sodium Channel Enac

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[OP.8C.04] THE FLOW DETECTION ROLE OF THE VASCULAR EPITHELIAL SODIUM CHANNEL (ENAC) IN AN EXPERIMENTAL MODEL OF HYPERTENSION

Journal of Hypertension ◽

10.1097/01.hjh.0000491602.51215.ac ◽

2016 ◽

Vol 34 ◽

pp. e103

Author(s):

Z. Ashley ◽

C. Leader ◽

I. Sammut ◽

F. McDonald ◽

R. Walker ◽

...

Keyword(s):

Sodium Channel ◽

Experimental Model ◽

Epithelial Sodium Channel ◽

Flow Detection ◽

Epithelial Sodium Channel Enac

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Apelin-13 Decreases Epithelial Sodium Channel (ENaC) Expression and Activity in Kidney Collecting Duct Cells

Cellular Physiology and Biochemistry ◽

10.33594/000000488 ◽

2022 ◽

Vol 56 (1) ◽

pp. 1-12

Keyword(s):

Sodium Channel ◽

Collecting Duct ◽

Water Channel ◽

Epithelial Sodium Channel ◽

Sodium Balance ◽

Principal Cells ◽

Wide Range ◽

Expression And Activity ◽

Epithelial Sodium Channel Enac

BACKGROUND/AIMS: Apelin and its G protein-coupled receptor APLNR (also known as APJ) are widely expressed within the central nervous system and peripheral organs including heart, lung and kidney. Several studies have shown that the apelin/APJ system is involved in various important physiological processes such as energy metabolism, cardiovascular functions and fluid homeostasis. In the kidney, the apelin/APJ system performs a wide range of activities. We recently demonstrated that apelin antagonises the hydro-osmotic effect of vasopressin on aquaporin-2 water channel (AQP-2) expression by reducing its mRNA and protein levels in collecting duct principal cells. The central role of these cells in water and sodium transport is governed by AQP-2 and the epithelial sodium channel (ENaC). The coordination of these channels is essential for the control of extracellular fluid volume, sodium homeostasis and blood pressure. This study aimed at investigating the role of apelin in the regulation of sodium balance in the distal nephron, and more specifically its involvement in modulating the expression and activity of ENaC in collecting duct principal cells. METHODS: mpkCCD cells were incubated in the presence of aldosterone and treated with or without apelin-13. Transepithelial Na+ current was measured and the changes in ENaC expression determined by RT-PCR and immunoblotting. RESULTS: Our data show that apelin-13 reduces the transepithelial sodium amiloride-sensitive current in collecting duct principal cells after 8h and 24h treatment. This effect was associated with a decrease in αENaC subunit expression and mediated through the ERK pathway as well as SGK1 and Nedd4-2. CONCLUSION: Our findings indicate that apelin is involved in the fine regulation of sodium balance in the renal collecting duct by opposing the effects of aldosterone, likely by activation of ENaC ubiquitination.

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Epithelial Sodium Channel and Salt-Sensitive Hypertension

Hypertension ◽

10.1161/hypertensionaha.120.14481 ◽

2021 ◽

Vol 77 (3) ◽

pp. 759-767

Author(s):

Stephanie M. Mutchler ◽

Annet Kirabo ◽

Thomas R. Kleyman

Keyword(s):

Blood Pressure ◽

Sodium Channel ◽

Salt Intake ◽

Extracellular Fluid ◽

Pressure Rise ◽

Epithelial Sodium Channel ◽

Sodium Reabsorption ◽

High Salt Intake ◽

Salt Sensitive Hypertension

The development of high blood pressure is influenced by genetic and environmental factors, with high salt intake being a known environmental contributor. Humans display a spectrum of sodium-sensitivity, with some individuals displaying a significant blood pressure rise in response to increased sodium intake while others experience almost no change. These differences are, in part, attributable to genetic variation in pathways involved in sodium handling and excretion. ENaC (epithelial sodium channel) is one of the key transporters responsible for the reabsorption of sodium in the distal nephron. This channel has an important role in the regulation of extracellular fluid volume and consequently blood pressure. Herein, we review the role of ENaC in the development of salt-sensitive hypertension, and present mechanistic insights into the regulation of ENaC activity and how it may accelerate sodium-induced damage and dysfunction. We discuss the traditional role of ENaC in renal sodium reabsorption and review work addressing ENaC expression and function in the brain, vasculature, and immune cells, and how this has expanded the implications for its role in the initiation and progression of salt-sensitive hypertension.

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