Interactive Actions of Aldosterone and Insulin on Epithelial Na<sup>+</sup> Channel Trafficking
Epithelial Na<sup>+</sup> channel (ENaC) participates in renal epithelial Na<sup>+</sup> reabsorption, controlling blood pressure. Aldosterone and insulin elevate blood pressure by increasing the ENaC-mediated Na<sup>+</sup> reabsorption. However, little informati...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-05-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/10/3407 |
| Summary: | Epithelial Na<sup>+</sup> channel (ENaC) participates in renal epithelial Na<sup>+</sup> reabsorption, controlling blood pressure. Aldosterone and insulin elevate blood pressure by increasing the ENaC-mediated Na<sup>+</sup> reabsorption. However, little information is available on the interactive action of aldosterone and insulin on the ENaC-mediated Na<sup>+</sup> reabsorption. In the present study, we tried to clarify if insulin would modify the aldosterone action on the ENaC-mediated Na<sup>+</sup> reabsorption from a viewpoint of intracellular ENaC trafficking. We measured the ENaC-mediated Na<sup>+</sup> 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 (<inline-formula> <math display="inline"> <semantics> <mrow> <msub> <mi>k</mi> <mi>I</mi> </msub> </mrow> </semantics> </math> </inline-formula>) 3.3-fold and the ENaC recycling rate (<inline-formula> <math display="inline"> <semantics> <mrow> <msub> <mi>k</mi> <mi>R</mi> </msub> </mrow> </semantics> </math> </inline-formula>) 2.0-fold, but diminished the ENaC degradation rate (<inline-formula> <math display="inline"> <semantics> <mrow> <msub> <mi>k</mi> <mi>D</mi> </msub> </mrow> </semantics> </math> </inline-formula>) 0.7-fold without any significant effect on the ENaC endocytotic rate (<inline-formula> <math display="inline"> <semantics> <mrow> <msub> <mi>k</mi> <mi>E</mi> </msub> </mrow> </semantics> </math> </inline-formula>); (B) under the insulin-unstimulated condition, aldosterone treatment decreased <inline-formula> <math display="inline"> <semantics> <mrow> <msub> <mi>k</mi> <mi>E</mi> </msub> </mrow> </semantics> </math> </inline-formula> 0.5-fold and increased <inline-formula> <math display="inline"> <semantics> <mrow> <msub> <mi>k</mi> <mi>R</mi> </msub> </mrow> </semantics> </math> </inline-formula> 1.4-fold, without any significant effect on <inline-formula> <math display="inline"> <semantics> <mrow> <msub> <mi>k</mi> <mi>I</mi> </msub> </mrow> </semantics> </math> </inline-formula> or <inline-formula> <math display="inline"> <semantics> <mrow> <msub> <mi>k</mi> <mi>D</mi> </msub> </mrow> </semantics> </math> </inline-formula>. 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. |
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| ISSN: | 1661-6596 1422-0067 |