Interactive Actions of Aldosterone and Insulin on Epithelial Na Channel Trafficking.

Epithelial Na channel (ENaC) participates in renal epithelial Na reabsorption, controlling blood pressure. Aldosterone and insulin elevate blood pressure by increasing the ENaC-mediated Na reabsorption. However, little information is available on the interactive action of aldosterone and insulin on the ENaC-mediated Na reabsorption. In the present study, we tried to clarify if insulin would modify the aldosterone action on the ENaC-mediated Na reabsorption from a viewpoint of intracellular ENaC trafficking. We measured the ENaC-mediated Na transport as short-circuit currents using a four-state mathematical ENaC trafficking model in renal A6 epithelial cells with or without aldosterone treatment under the insulin-stimulated and -unstimulated conditions. We found that: (A) under the insulin-stimulated condition, aldosterone treatment (1 µM for 20 h) significantly elevated the ENaC insertion rate to the apical membrane ( k I ) 3.3-fold and the ENaC recycling rate ( k R ) 2.0-fold, but diminished the ENaC degradation rate ( k D ) 0.7-fold without any significant effect on the ENaC endocytotic rate ( k E ); (B) under the insulin-unstimulated condition, aldosterone treatment decreased k E 0.5-fold and increased k R 1.4-fold, without any significant effect on k I or k D . Thus, the present study indicates that: (1) insulin masks the well-known inhibitory action of aldosterone on the ENaC endocytotic rate; (2) insulin induces a stimulatory action of aldosterone on ENaC apical insertion and an inhibitory action of aldosterone on ENaC degradation; (3) insulin enhances the aldosterone action on ENaC recycling; (4) insulin has a more effective action on diminution of ENaC endocytosis than aldosterone.