Amiloride-sensitive Na⁺ channels belong to the epithelial Na⁺ channel (ENaC)-degenerin superfamily of ion channels. In addition to their key role in sodium handling, they serve diverse functions in many tissues. Improper functioning of ENaC has been implicated in several diseases, including salt-sensitive hypertension (Liddle’s syndrome), salt-wasting syndrome (pseudohypoaldosteronism type I), pulmonary edema, and cystic fibrosis. We have utilized planar lipid bilayers, a well-defined system that allows simultaneous control of “internal” and “external” solutions, to study ENaCs.