THE HETEROTETRAMERIC ARCHITECTURE OF THE EPITHELIAL SODIUM-CHANNEL (ENAC)

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.