Premium
ANK3 Knockout Reduces ENaC Activity and Slows Adaptation to a Na + Free Diet
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.624.6
Subject(s) - epithelial sodium channel , endocrinology , medicine , knockout mouse , excretion , chemistry , aldosterone , phosphorylation , sodium , biology , biochemistry , receptor , 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. We recently showed that phosphorylation of ENaC by CK2 in a putative ANK3 binding domain regulates ENaC activity. Therefore we tested the necessity and sufficiency of ANK3 for normal ENaC function. We produced tissue specific ANK3 knockout mice in the aldosterone sensitive distal nephron. Knockout was verified by immunohistochemistry. Split open tubule recordings from these mice showed significantly decreased baseline ENaC activity. The mice displayed a longer adaptation period to a sodium free diet, and a significantly different response to TBB, a casein‐kinase II inhibitor, compared to control. Together these results suggest that ANK3 modulates ENaC activity by interacting with CK2 phosphorylation sites in Beta and Gamma ENaC. In future work we will examine the mechanism by which this interaction modifies ENaC activity. 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 .