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Extracellular protons activate human ENaC by relieving sodium self‐inhibition
Author(s) -
Collier Daniel M,
Snyder Peter M
Publication year - 2008
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.22.1_supplement.934.10
Subject(s) - epithelial sodium channel , amiloride , extracellular , chemistry , sodium , xenopus , biophysics , sodium channel , acid sensing ion channel , ion channel , biochemistry , biology , receptor , organic chemistry , gene
The Epithelial Sodium Ion Channel (ENaC) is exposed to a wide range of proton concentrations in the kidney and lung. We tested whether protons alter ENaC activity. In Xenopus oocytes expressing human αβγENaC, amiloride sensitive current was altered by pH in the physiologically relevant range (pH 8.5‐6.0) with a pH 50 of 7.2. Compared to pH 7.4, pH 8.5 decreased current by 18.4%, whereas changing to pH 6.5 increased current by 29.7%. We hypothesized that pH might regulate ENaC by altering sodium self‐inhibition. Consistent with this hypothesis, we found that external sodium was required for pH to alter ENaC outward current. Moreover, we found that the response to pH was altered by mutations in the extracellular domain that disrupt sodium self‐inhibition. αH255R increased sodium self‐inhibition and caused an increase in the size of the pH activated currents. Conversely, γH233R, which decreased sodium self‐inhibition, was insensitive to external pH. Our results suggest that protons activate human ENaC in part by relieving sodium self‐inhibition.