Oxygen regulation of the epithelial Na channel in the collecting duct.

Abstract

The PO(2) within the kidney changes dramatically from cortex to medulla. The present experiments examined the effect of changing PO(2) on epithelial Na channel (ENaC)-mediated Na transport in the collecting duct using the mpkCCD-c14 cell line. Decreasing ambient O(2) concentration from 20 to 8% decreased ENaC activity by 40%; increasing O(2) content to 40% increased ENaC activity by 50%. The O(2) effect required several hours to develop and was not mimicked by the acid pH that developed in monolayers incubated in low-O(2) medium. Corticosteroids increased ENaC activity at each O(2) concentration; there was no interaction. The pathways for O(2) and steroid regulation of ENaC are different since O(2) did not substantially affect Sgk1, α-ENaC, Gilz, or Usp2-45 mRNA levels, genes involved in steroid-mediated ENaC regulation. The regulation of ENaC activity by these levels of O(2) appears not to be mediated by changes in hypoxia-inducible factor-1α or -2α activity or a change in AMP kinase activity. Changes in O(2) concentration had minimal effect on α- or γ-ENaC mRNA and protein levels; there were moderate effects on β-ENaC levels. However, 40% O(2) induced substantially greater total β- and γ-ENaC on the apical surface compared with 8% O(2); both subunits demonstrated a greater increase in the mature forms. The α-ENaC subunit was difficult to detect on the apical surface, perhaps because our antibodies do not recognize the major mature form. These results identify a mechanism of ENaC regulation that may be important in different regions of the kidney and in responses to changes in dietary NaCl.

• Authors: Russell F Husted, Hongyan Lu, Rita D Sigmund, John B Stokes
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 300 Issue 2 Pg. F412-24 (Feb 2011) ISSN: 1522-1466 [Electronic] United States
• PMID: 21123494 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Adrenal Cortex Hormones
• Basic Helix-Loop-Helix Transcription Factors
• Epithelial Sodium Channels
• Hypoxia-Inducible Factor 1
• endothelial PAS domain-containing protein 1
• Adenylate Kinase
• Oxygen

Topics

• Adenylate Kinase (metabolism)
• Adrenal Cortex Hormones (pharmacology)
• Animals
• Basic Helix-Loop-Helix Transcription Factors (metabolism)
• Cell Line
• Epithelial Sodium Channels (drug effects, metabolism)
• Humans
• Hydrogen-Ion Concentration
• Hypoxia-Inducible Factor 1 (metabolism)
• Kidney Tubules, Collecting (drug effects, metabolism)
• Mice
• Oxygen (metabolism)