ENaCdependent

ENaCdependent describes processes that rely on the epithelial sodium channel (ENaC) to mediate sodium uptake across epithelia, enabling transepithelial Na+ transport and volume regulation. ENaC is expressed in kidney collecting ducts, colon, sweat and salivary glands, and in the lungs where it participates in airway liquid clearance. The channel is a heterotrimer of α, β, and γ subunits; amiloride-sensitive and selectively permeable to Na+ with low conductance to other ions.

Regulation: Aldosterone increases ENaC transcription and membrane abundance via mineralocorticoid receptor signaling, including SGK1 and inhibition of NEDD4-2 ubiquitin ligase, reducing ENaC endocytosis. ENaC activity is also enhanced by proteolytic cleavage of the γ subunit by serine proteases such as furin and prostasin, which increases open probability. Cortisol can substitute for aldosterone in some tissues with 11β-HSD2 protection.

Physiological role: In the kidney, ENaC-dependent Na+ reabsorption in the collecting duct contributes to final urine Na+ excretion, extracellular fluid volume, and blood pressure regulation. In colon, ENaC participates in Na+ uptake; in lungs, ENaC drives alveolar fluid clearance. ENaC activity is also involved in sweat and vocal fold hydration.

Clinical significance: Mutations causing ENaC gain-of-function lead to Liddle syndrome, with hypertension and hypokalemia; loss-of-function mutations cause pseudohypoaldosteronism type 1, with salt wasting, hyperkalemia, and hypotension. Pharmacologically, ENaC blockers such as amiloride and triamterene are used as potassium-sparing diuretics and in treatment of conditions with ENaC overactivity.

This term is used in physiology and pathology to denote processes sensitive to or dependent on ENaC activity, and context-dependent regulation by hormonal, proteolytic, and ubiquitin-mediated pathways.