Epithelial Sodium Channel

Abstract

Despite large changes in water and salt intake, the kidney is able to maintain the extracellular osmolarity and volume within narrow margins.1 Such fine control requires specific factors or hormones; among them, aldosterone and vasopressin play key roles. In aldosterone-responsive epithelial cells (kidney, colon), the epithelial sodium channel (ENaC) plays a critical role in the control of sodium balance, blood volume, and blood pressure.1 Tissue-specific expression of ENaC is observed in sodium transporting epithelia (lung, intestine, kidney, and exocrine and sweat glands). In lung, ENaC has a distinct role in controlling the ionic composition of the air liquid interface and thus the rate of mucociliary transport. ENaC subunits are found in the aldosterone-sensitive distal nephron (ASDN; Figure), in the surface epithelia of the colon, and in the duct cells of exocrine glands. In human, imbalance of ENaC activity in aldosterone target cells leads to a large variety of pathologies:2 loss of function of ENaC leads to a severe renal salt loosing syndrome, with a hypotensive phenotype (pseudohypoaldosteronism type 1), whereas ENaC gain of function leads to hypertension (Liddle’s syndrome). Figure. Model of aldosterone action in the principal cell of the ASDN. Aldosterone binds to its cognate mineralocorticoid receptor (MR) and is translocated into the nucleus, where it binds to the promoter of specific genes leading to the repression (ART) or induction (AIT) of mRNA transcripts (ENaC, NaK-ATPase, and Sgk-1). Sgk-1, in turn, regulates the activity of E3 ubiquitin ligase (Nedd4-2), leading to increased ENaC activity at the cell surface.1 The purpose of this brief review is to discuss recent developments pertaining to the role of ENaC in hypertension. We focus on the role of ENaC in Liddle’s syndrome, a mendelian form of hypertension, and essential hypertension. ### Human Disease Liddle’s syndrome is an autosomal dominant form of salt-sensitive hypertension, …