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ENaC activation by bile acids depends on specific moieties, but not on membrane permeability
Author(s) -
Wang XuePing,
Im Seohyun Janice,
Ertem Merve,
Balchak Deidra M,
Montalbetti Nicolas,
Carattino Marcelo D,
Ray Evan C,
Kashlan Ossama B
Publication year - 2019
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.2019.33.1_supplement.751.16
Subject(s) - epithelial sodium channel , xenopus , bile acid , chemistry , extracellular , cholangiocyte , apical membrane , amino acid , bile duct , medicine , biochemistry , microbiology and biotechnology , endocrinology , membrane , sodium , biology , organic chemistry , gene
The epithelial sodium channel (ENaC) mediates Na + transport in several epithelia, including the aldosterone‐sensitive distal nephron, distal colon, and biliary epithelium. Numerous factors regulate the activity of the channel, including extracellular ligands, post‐translational modifications, and membrane‐resident lipids. Bile acids are abundant in the biliary tree and intestinal tract, and can be elevated in the urine of patients with advanced liver disease. Using Xenopus oocytes, we found that bile acids both activated and inhibited mouse ENaC, dependent on the bile acid. Whether bile acids were activating or inhibiting depended on the position and stereochemistry of specific moieties. Taurine conjugated bile acids had stronger effects than their more membrane permeant unconjugated counterparts, suggesting that bile acids regulate ENaC extracellularly. Bile acids that increased ENaC currents had a hydroxyl group at position 12, facing the hydrophilic side. Bile acids that decreased ENaC currents had a hydroxyl group at position 6. Bile acid dependent activation of ENaC currents was mildly voltage‐dependent, suggesting that regulation occurs in the outer leaflet of the membrane. Bile acids also regulated ENaC in a cortical collecting duct cell line, mirroring results in Xenopus oocytes. These results suggest that bile acids interact directly with ENaC near the interface between the outer leaflet and the extracellular solution. Support or Funding Information This work was supported by NIDDK, National Institutes of Health, Grant R01 DK098204 (to O.B.K), and a grant from the Pittsburgh Liver Research Center. The Pittsburgh Center for Kidney Research was supported by Grant DK P30 DK079307 from NIDDK, National Institutes of Health. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .