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Regulation of ENaC by Casein Kinase II
Author(s) -
Berman Jonathan Max,
Mironova Elena,
Stockand James
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.624.7
Subject(s) - epithelial sodium channel , casein kinase 2 , phosphorylation , endocrinology , medicine , excretion , chemistry , natriuresis , ion channel , sodium , biology , protein kinase a , biochemistry , receptor , mitogen activated protein kinase kinase , organic chemistry
The Epithelial Na + Channel, ENaC, is the final arbiter of sodium excretion in the kidneys. As such, discretionary control of ENaC by hormones is critical to the fine‐tuning of electrolyte and water excretion and consequently, blood pressure. Casein kinase 2 (CK2) phosphorylates ENaC. Phosphorylation by CK2 is necessary for normal ENaC activity. We tested the physiological importance of CK2 regulation of ENaC as the degree to which ENaC activity is dependent on CK2 phosphorylation in the living organism is unknown. This was addressed using patch clamp analysis of ENaC in split‐open collecting ducts in complement with whole animal physiological studies of sodium excretion in mice. We also used ENaC harboring CK2 phosphorylation site mutations to elaborate mechanism. We found that ENaC activity in ex vivo preparations of murine collecting duct had a significant decrease in activity in response to selective antagonism of CK2. In whole animal experiments selective antagonism of CK2 caused a natriuresis similar to benzamil, but not additive to benzamil, suggesting an ENaC dependent mechanism. Regulation of ENaC by CK2 was abolished by mutation of the canonical CK2 phosphorylation sites in beta and gamma ENaC. Together, these results demonstrate that the appropriate regulation of ENaC by CK2 is necessary for the normal physiological role played by this key renal ion channel in the fine‐tuning of sodium excretion. Support or Funding Information This research was supported by American Heart Association grants 15GRNT22930030 & 17GRNT3292002 (to JDS), and 17POST33660468 (to JMB), and National Institutes of Health grants T32HL00744536A1 (to JDS and JMB), K12GM111726 (to JMB), and F32DK104572 (to EM). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .