Figure 5.

Mechanisms that regulate electrogenic absorption of sodium across epithelial cells. Sodium ions are taken up via the apical epithelial sodium channel (ENaC) and exit the cell via the basolateral Na⁺, K⁺ ATPase. The activity of ENaC can be reduced by agonists binding to receptors that stimulate mobilization of intracellular calcium stores. Elevations in intracellular sodium activate the ubiquitin ligase, Nedd4-2, which in turn triggers the internalization and degradation of ENaC. Agonists binding to receptors that elevate intracellular cAMP stimulate ENaC activity both directly, and by inhibiting Nedd4-2 activity. For additional details, see text.