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, ?-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-1? or -2? activity or a change in AMP kinase activity. Changes in O(2) concentration had minimal effect on ?- or ?-ENaC mRNA and protein levels; there were moderate effects on ?-ENaC levels. However, 40% O(2) induced substantially greater total ?- and ?-ENaC on the apical surface compared with 8% O(2); both subunits demonstrated a greater increase in the mature forms. The ?-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.

SUBMITTER: Husted RF 

PROVIDER: S-EPMC3044001 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature