Effects of Lipids on ENaC Activity in Cultured Mouse Cortical Collecting Duct Cells |
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Authors: | Su Wang Fei Meng Jingyuan Xu Yuchun Gu |
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Institution: | (1) Department of Physiology, University of Birmingham, Edgbaston, B15 2TT, UK |
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Abstract: | Direct effects on epithelial Na+ channels (ENaC) activity by lipids, e.g., arachidonic acid (AA), eicosatetraynoic acid (ETYA), linoleic acid (LA), stearic
acid (SA), hydroxyeicosatetraenoic acid (HETE), 11,12–epoxyeicosatrienoic acid (EET), (PGF2), and (PGE2), in cultured mouse
cortical collecting duct (M1) cells were clarified by using single-channel recordings in this study. In a cell-attached recording,
a bath application of 10 μM AA significantly reduced the ENaC open probability (NPo), whereas 10 μM ETYA or 5 μM LA only induced
a slight inhibition. The inside-out recording as a standard protocol was thereafter performed to examine effects of these
lipids on ENaC activity. Within 10 min after the formation of the inside-out configuration, the NPo of ENaC in cultured mouse
cortical collecting duct (M1) cells remained relatively constant. Application of ETYA or LA or SA exhibited a similar inhibition
on the channel NPo when applied to the extracellular side, suggesting that fatty acids could exert a nonspecific inhibition
on ENaC activity. 11,12-EET, a metabolite of AA via the cytochrome P450 epoxygenase pathway, significantly inhibited the ENaC
NPo, whereas 20-HETE, a metabolite of AA via the hydroxylase pathway, only caused a small inhibition of the ENaC NPo, to a
similar degree as that seen with ETYA and LA. However, both PGE2 and PGF2α significantly enhanced the ENaC NPo. These results
suggest that fatty acids exert a nonspecific effect on ENaC activity due to the interaction between the channel proximity
and the lipid. The opposite effects of 11,12-EET and prostaglandin (PG) implicate different mechanisms in regulation of ENaC
activity by activation of epoxygenase and cyclooxygenase. |
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Keywords: | ENaC AA ETYA EET PG |
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