Thumb domains of the three epithelial Na+ channel subunits have distinct functionsThe epithelial Na+ channel (ENaC) possesses a large extracellular domain formed by a β-strand core enclosed by three peripheral α-helical subdomains, which have been dubbed thumb, finger, and knuckle. Here we asked whether the ENaC thumb domains play specific roles in channel function. To this end, we examined the characteristics of channels lacking a thumb domain in an individual ENaC subunit (α, β, or γ). Removing the γ subunit thumb domain had no effect on Na+ currents when expressed in Xenopus oocytes, but moderately reduced channel surface expression.
Functional Roles of Clusters of Hydrophobic and Polar Residues in the Epithelial Na+ Channel Knuckle DomainBackground: There are regulatory interactions between ENaC and extracellular factors.Results: Mutations of multiple α subunit knuckle residues activate ENaC by suppressing the inhibitory effect of Na+. Channels lacking the β or γ subunit knuckle have processing defects.Conclusion: Interactions between the α subunit knuckle and palm/finger domains regulate ENaC.Significance: Intrasubunit domain-domain interactions have important regulatory roles.