Abstract
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 () 3.3-fold and the ENaC recycling rate () 2.0-fold, but diminished the ENaC degradation rate () 0.7-fold without any significant effect on the ENaC endocytotic rate (); (B) under the insulin-unstimulated condition, aldosterone treatment decreased 0.5-fold and increased 1.4-fold, without any significant effect on or . 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.
Highlights
The transepithelial Na+ transport mediated via epithelial Na+ channel (ENaC) participates in various bodily functions including regulation of blood pressure, the amount of body fluid content, and the lung alveolar fluid clearance [1,2,3,4,5,6,7,8,9,10,11,12,13]
We evaluated the amounts of ENaC in the insertion state, the apical membrane state, the recycling state and the degradation state (Figure 3): Insert (t), the amount of ENaC in the insertion state (Insert) at time = t; Apical (t), the amount of ENaC in the apical membrane state (Apical) at time = t; Recycl (t), the amount of ENaC in the recycling state (Recycl) at time = t; Degrad (t), the amount of ENaC in the degradation state (Degrad) at time = t; t is the time after basolateral application of insulin
We studied the aldosterone action on the cumulative time (TCTAM) how long an individual ENaC stayed in the apical membrane before degradation, reflecting the cumulative Na+ absorption (see Equation (17) and Table 3): TCTAM
Summary
The transepithelial Na+ transport mediated via epithelial Na+ channel (ENaC) participates in various bodily functions including regulation of blood pressure, the amount of body fluid content, and the lung alveolar fluid clearance [1,2,3,4,5,6,7,8,9,10,11,12,13] This ENaC-mediated transepithelial Na+ transport requires two steps across the apical and basolateral membranes of epithelial cells: (1) the first step is the entry of Na+ across the apical membrane of epithelial cells into the intracellular space via ENaC expressed in the apical membrane, and (2) the second step is the extrusion of Na+ from the intracellular space across the basolateral membrane of epithelial cells mediated by the Na+,K+-pump located in the basolateral membrane [8,9]. EoWNceyaChtoeurtesicirnegrpatohtreet;feos(rt2a)tbhlieinsfhsierusdtliftnoimuiren-stdthauetecinmetseartaahcetsmitviaemtiaccuatliloamntooodrfeyal lodafocistntiteorranocneoellfuanlaadlrdosterone on ENaC ainpsiuclianl oinn stehertiinotnracaenlldulaarnENinahCibtriatfofircykinagctpiroonceossf: a(1l)dionssutelirnomneaskosnthEeNwaeCll-kdneogwrnadinahtibioitnor;y(3) insulin enhances tahcteionaldofoasltdeorsotenroenaecotniotnheoEnNEaNC aenCdorceyctyotciclinragte;;a(n2)din(s4u)liinnsinudluinceshasstaimmuloatroeryeffacetciotnivoef action on diminutionaldoofstEeNronaeConenEdNoaCcyatpoiscaisl itnhsearntioanldanodstaenroinnheib.itory action of aldosterone on ENaC degradation;
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