ESR1

Overview

The Epithelial Sodium Channel (ENaC) is a membrane-bound ion channel that is highly selective for sodium ions (Na⁺). It plays a crucial role in the regulation of sodium balance, blood pressure, and fluid homeostasis in the body. ENaC is primarily located in the epithelial cells of the kidney, lung, and colon, where it facilitates the reabsorption of sodium ions from the lumen into the cells.

Structure

ENaC is a heterotrimeric protein composed of three homologous subunits: α, β, and γ. Each subunit is encoded by a separate gene, and the proper assembly of these subunits is essential for the channel's function. The channel is part of the ENaC/DEG superfamily, which includes other ion channels involved in mechanosensation and osmoregulation.

Function

ENaC is responsible for the passive transport of sodium ions across the apical membrane of epithelial cells. This process is driven by the electrochemical gradient established by the Na⁺/K⁺-ATPase pump located on the basolateral membrane. The activity of ENaC is regulated by several factors, including hormones such as aldosterone and vasopressin, as well as intracellular signaling pathways.

Regulation

The regulation of ENaC is complex and involves multiple mechanisms:

• Hormonal Regulation: Aldosterone increases the expression and activity of ENaC by promoting the transcription of its subunits and enhancing the channel's insertion into the membrane.
• Proteolytic Activation: ENaC can be activated by proteolytic cleavage of its extracellular domains by proteases such as furin and prostasin.
• Ubiquitination and Endocytosis: The channel can be downregulated by ubiquitination, which targets it for endocytosis and degradation.

Clinical Significance

Mutations in the genes encoding ENaC subunits can lead to disorders of sodium balance. For example, gain-of-function mutations can cause Liddle syndrome, characterized by hypertension due to excessive sodium reabsorption. Conversely, loss-of-function mutations can result in pseudohypoaldosteronism type 1, a condition marked by salt wasting and hypotension.

Research and Therapeutic Implications

ENaC is a target for diuretic drugs such as amiloride, which inhibit the channel and are used to treat conditions like hypertension and edema. Understanding the regulation and function of ENaC is crucial for developing new therapeutic strategies for diseases related to sodium imbalance.

Also see

• Sodium channel
• Ion channel
• Aldosterone
• Liddle syndrome
• Pseudohypoaldosteronism

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