Epithelial Na+ channel (ENaC) function is regulated by the intracellular Na+ concentration ((Na+)i) through a process known as Na+ feedback inhibition. Although this process is known to decrease the expression of proteolytically processed active channels on the cell surface, it is unknown how (Na+)i alters ENaC cleavage. We show here that (Na+)i regulates the posttranslational processing of ENaC subunits during channel biogenesis. At times when (Na+)i is low, ENaC subunits develop mature N-glycans and are processed by proteases.
