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 ([Formula: see text]) 3.3-fold and the ENaC recycling rate ([Formula: see text]) 2.0-fold, but diminished the ENaC degradation rate ([Formula: see text]) 0.7-fold without any significant effect on the ENaC endocytotic rate ([Formula: see text]); (B) under the insulin-unstimulated condition, aldosterone treatment decreased [Formula: see text] 0.5-fold and increased [Formula: see text] 1.4-fold, without any significant effect on [Formula: see text] or [Formula: see text]. 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.