Epithelial sodium channels (ENaC)

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).


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The epithelial sodium channels (ENaC) mediates sodium reabsorption in the aldosterone-sensitive distal part of the nephron and the collecting duct of the kidney. ENaC is assembled as a heterotrimer composed of three homologous subunits α, β, and γ or δ, β, and γ [12]. These subunits consitute a family within the ENaC/Degenerin super-family [12]. Genes encoding ENaC subunits are found in all vertebrates with the exception of ray-finned fishes [12]. ENaC composed of α, β, and γ subunits is located mostly in tight or high-resistance epithelial tissues such as the airways, distal colon and exocrine glands [7]. ENaC activity is tightly regulated in the kidney by aldosterone, angiotensin II (AGT, P01019), vasopressin (AVP, P01185), insulin (INS, P01308) and glucocorticoids; this fine regulation of ENaC is essential to maintain sodium balance between daily intake and urinary excretion of sodium, circulating volume and blood pressure. ENaC expression is also vital for clearance of foetal lung fluid, and to maintain air-surface-liquid [13,17]. Sodium reabsorption is suppressed by the ‘potassium-sparing’ diuretics amiloride and triamterene. ENaC is a heteromultimeric channel made of homologous α β and γ subunits. The primary structure of the α ENaC subunit was identified by expression cloning [4,12]; β and γ ENaC subunits were identified by functional complementation of the α subunit [5,12]. Each ENaC subunit contains 2 TM α helices connected by a large extracellular loop and short cytoplasmic amino- and carboxy-termini. The stoichiometry of the epithelial sodium channel in the kidney and related epithelia is, by homology with the structurally related channel ASIC1a, thought to be a heterotrimer of 1α:1β:1γ subunits [10].

Channels and Subunits


ENaCαβγ Show summary » More detailed page


ENaC α Show summary » More detailed page

ENaC β Show summary » More detailed page

ENaC δ Show summary » More detailed page

ENaC γ Show summary » More detailed page


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Further reading

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NC-IUPHAR subcommittee and family contributors

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How to cite this family page

Database page citation:

Israel Hanukoglu. Epithelial sodium channels (ENaC). Accessed on 20/01/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=122.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Peters JA, Kelly E, Marrion N, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Ligand-gated ion channels. Br J Pharmacol. 172: 5870-5903.