Epithelial sodium channel, salt intake, and hypertension

Abstract

The epithelial sodium channel (ENaC) is a membrane protein made of three different but homologous subunits (a, b, and g) present in the apical membrane of epithelial cells of, for example, the distal nephron. This channel is responsible for salt reabsorption in the kidney and can cause human diseases by increasing channel function in Liddle's syndrome, a form of hereditary hypertension, or by decreasing channel function in pseudohypoaldosteronism type I, a salt-wasting disease in infancy. This review briefly discusses recent advances in understanding the implication of ENaC in Liddle's syndrome and in pseudohypoaldosteronism type I, both caused by mutations in the SCNN1 (ENaC) genes. Furthermore, it is still an open question to which extent SCNN1 genes coding for ENaC might be implicated in essential hypertension. The development of Scnn1 genetically engineered mouse models will provide the opportunity to test the effect of environmental factors, like salt intake, on the development of this kind of salt- sensitive hypertension.

Aldosterone Regulates MicroRNAs in the Cortical Collecting Duct to Alter Sodium Transport

“…9 In humans there is a direct link between defective ENaC physiology and disease in Liddle syndrome (hypertension) and pseudohypoaldosteronism (hypotension). 5,[10][11][12][13][14][15][16] ENaC is regulated by several intrinsic and external factors, the details of which have been reviewed previously. 3,4,10,17,18 An essential ENaC regulator is the mineralocorticoid hormone aldosterone, which is central to Na + homeostasis.…”

Hsp70 Promotes Epithelial Sodium Channel Functional Expression by Increasing Its Association with Coat Complex II and Its Exit from Endoplasmic Reticulum

“…In the absence of ENaC, salt wasting can occur in the kidneys, leading to hypotension and a condition known as pseudohypoaldosteronism type 1 (2). In contrast, patients with Liddle syndrome have salt-sensitive hypertension, which results from ENaC functional overexpression in the distal nephron (2)(3)(4)(5). In addition to its critical role in blood pressure regulation, ENaC also plays an important role in the airway epithelia.…”

Insulin-induced phosphorylation of ENaC correlates with increased sodium channel function in A6 cells

“…Together, our findings suggest that ENaC activity is controlled by subunit phosphorylation in cells that endogenously express the channel and the machinery for hormonal stimulation of sodium transport. epithelial sodium channel; aldosterone; sodium transport IT IS NOW WIDELY ACCEPTED that the epithelial sodium channel (ENaC), located in the cortical collecting duct of the renal tubule, plays a major role in preserving sodium balance (9). Although substantial progress has been made in understanding ENaC regulation at the molecular level, there are fewer insights into the cascade of molecular events that link activation of cell membrane receptors or intracellular receptors, such as the mineralocorticoid receptor, to the activation of ENaC located in the apical membrane of epithelial cells.…”