Intrinsic voltage dependence of the epithelial Na+ channel is masked by a conserved transmembrane domain tryptophan.

ABSTRACT: Tryptophan residues critical to function are frequently located at the lipid-water interface of transmembrane domains. All members of the epithelial Na+ channel (ENaC)/Degenerin (Deg) channel superfamily contain an absolutely conserved Trp at the base of their first transmembrane domain. Here, we test the importance of this conserved Trp to ENaC/Deg function. Targeted substitution of this Trp in mouse ENaC and rat ASIC subunits decrease channel activity. Differential substitution with distinct amino acids in alpha-mENaC shows that it is loss of this critical Trp rather than introduction of residues having novel properties that changes channel activity. Surprisingly, Trp substitution unmasks voltage sensitivity. Mutant ENaC has increased steady-state activity at hyperpolarizing compared wit

SUBMITTER: Pochynyuk O 

PROVIDER: S-EPMC2757952 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature