The epithelial sodium channel (ENaC) is a key element for the maintena
nce of sodium balance and the regulation of blood pressure, Three homo
logous ENaC subunits (alpha, beta and gamma) assemble to form a highly
Na+- selective channel, However, the subunit stoichiometry of ENaC ha
s not yet been solved, Quantitative analysis of cell surface expressio
n of ENaC alpha, beta and gamma subunits shows that they assemble acco
rding to a fixed stoichiometry, with alpha ENaC as the most abundant s
ubunit, Functional assays based on differential sensitivities to chann
el blockers elicited by mutations tagging each a, beta and gamma subun
it are consistent with a four subunit stoichiometry composed of two al
pha, one beta and one gamma, Expression of concatameric cDNA construct
s made of different combinations of ENaC subunits confirmed the four s
ubunit channel stoichiometry and showed that the arrangement of the su
bunits around the channel pore consists of two alpha subunits separate
d by beta and gamma subunits.