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Ethanol Stimulates Epithelial Sodium Channels via Reactive Oxygen Species
Author(s) -
Bao HuiFang,
Ma HePing,
Eaton Douglas C
Publication year - 2011
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.25.1_supplement.1041.44
Subject(s) - chemistry , acetaldehyde , epithelial sodium channel , reactive oxygen species , ethanol , intracellular , biochemistry , sodium , biophysics , biology , organic chemistry
Disorders of electrolyte and water metabolism with resultant retention of sodium and water are common in alcoholics. However, the mechanisms responsible are largely unknown. In the present study, we found that ethanol stimulates the epithelial Na + channel (ENaC) in A6 distal nephron cells. The data from cell‐attached patch‐clamp experiments showed that ethanol significantly increased both ENaC open probability (P o ) and the number of active ENaC in the patch ( N ). The effects were mimicked by acetaldehyde, the first metabolic product of ethanol, as well as by n‐propanol, another primary alcohol which can be oxidized to form an aldehyde, but not by iso‐propanol, a secondary alcohol which can also be oxidized, but which forms a ketone rather than an aldehyde. Confocal microscopy combined with biotinylation experiments showed that ethanol significantly increased α‐ENaC protein in the apical membrane. Primary alcohols and acetaldehyde elevated intracellular reactive oxygen species (ROS). The effects of ethanol on ENaC P o and N were abolished by a superoxide dismutase mimetic compound, 4‐hydroxy‐2,2,6,6‐tetramethylpiperidinyloxy (TEMPOL). Together with our previous finding that ROS stimulate ENaC, these results suggest that ethanol stimulates ENaC by elevating intracellular ROS probably via its metabolic product acetaldehyde. Supported by 2R01DK067110 to HPM, P01 DK061521, R37 DK037963, and P50 AA013757 to DCE