Nomenclature	Subunits	Activators (EC50)	Channel Blockers (IC50)	Functional characteristics
ENaCαβγ	ENaC α, ENaC β, ENaC γ	S3969 (1.2x10-6 M) 200	P552-02 (7.6x10-9 M), benzamil (∼1x10-8 M), amiloride (1x10-7 – 2x10-7 M), triamterene (∼5x10-6 M) 189,196	γ ≈ 4–5 pS, PNa/PK > 20; tonically open at rest; expression and ion flux regulated by circulating aldosterone-mediated changes in gene transcription. The action of aldosterone, which occurs in ‘early’ (1.5–3 h) and ‘late’ (6–24 hr) phases is competitively antagonised by spironolactone, its active metabolites and eplerenone. Glucocorticoids are important functional regulators in lung/airways and this control is potentiated by thyroid hormone; but the mechanism underlying such potentiation is unclear 185,206,209. The density of channels in the apical membrane, and hence GNa, can be controlled via both serum and glucocorticoid-regulated kinases (SGK1, 2 and 3) 190,191 and via cAMP/PKA 203; and these protein kinases appear to act by inactivating Nedd-4/2, a ubiquitin ligase that normally targets the ENaC channel complex for internalization and degradation 186,190. ENaC is constitutively activated by soluble and membrane-bound serine proteases, such as furin, prostasin (CAP1), plasmin and elastase 197,198,204,207,208. The activation of ENaC by proteases is blocked by a protein, SPLUNC1, secreted by the airways and which binds specifically to ENaC to prevent its cleavage 192. Pharmacological inhibitors of proteases (e.g. camostat acting upon prostasin) reduce the activity of ENaC 202. Phosphatidylinositides such as PtIns(4,5)P2 and PtIns(3,4,5)P3) stabilise channel gating probably by binding to the β and γ ENaC subunits, respectively 201,205, whilst C terminal phosphorylation of β and γ-ENaC by ERK1/2 has been reported to inhibit the withdrawal of the channel complex from the apical membrane 212. This effect may contribute to the cAMP-mediated increase in sodium conductance.