Abstract
The epithelial sodium channel (ENaC) forms a pathway for transpepithelial Na+ transport in a variety of epithelial tissues including the kidney collecting duct, airway epithelium, and distal colon. In the kidney, ENaC plays a crucial role in body Na+ content and blood pressure control; abnormalities in ENaC function lead to several diseases such as Liddle’s syndrome and pseudohypoaldosteronism. Recent studies have revealed that ENaC function in epithelia is mainly regulated through membrane trafficking controlling the number of channels at the surface of the apical membrane. Apical membrane expression of ENaC is regulated through multiple steps, including synthesis, exocytosis, endocytosis, recycling, and degradation. Hormones such as aldosterone and vasopressin increase ENaC delivery to the apical surface by regulating those steps. This review discusses current understanding of molecular mechanisms of ENaC trafficking and introduces a newly-observed phenomenon that suggests the existence of undiscovered regulatory mechanisms of membrane trafficking: dependence of recycling rate constants on total ENaC amounts in recycle.