Open AccessRegulating ENaC’s gate
Author(s) -
Thomas R. Kleyman,
Douglas C. Eaton
Publication year - 2020
Publication title -
american journal of physiology. cell physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.432
H-Index - 181
eISSN - 1522-1563
pISSN - 0363-6143
DOI - 10.1152/ajpcell.00418.2019
Subject(s) - epithelial sodium channel , extracellular , ion channel , palmitoylation , acid sensing ion channel , proteases , chemistry , biophysics , microbiology and biotechnology , biochemistry , biology , cysteine , enzyme , receptor , organic chemistry , sodium
Epithelial Na + channels (ENaCs) are members of a family of cation channels that function as sensors of the extracellular environment. ENaCs are activated by specific proteases in the biosynthetic pathway and at the cell surface and remove embedded inhibitory tracts, which allows channels to transition to higher open-probability states. Resolved structures of ENaC and an acid-sensing ion channel revealed highly organized extracellular regions. Within the periphery of ENaC subunits are unique domains formed by antiparallel β-strands containing the inhibitory tracts and protease cleavage sites. ENaCs are inhibited by Na + binding to specific extracellular site(s), which promotes channel transition to a lower open-probability state. Specific inositol phospholipids and channel modification by Cys-palmitoylation enhance channel open probability. How these regulatory factors interact in a concerted manner to influence channel open probability is an important question that has not been resolved. These various factors are reviewed, and the impact of specific factors on human disorders is discussed.