Membrane Tension Modulates the Effects of Apical Cholesterol on the Renal Epithelial Sodium Channel |
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Authors: | Shi-Peng Wei Xue-Qi Li Chu-Fang Chou You-You Liang Ji-Bin Peng David G Warnock He-Ping Ma |
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Institution: | (1) Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, 1530 Third Avenue South, Zeigler Research Building 510, Birmingham, AL 35294, USA;(2) Department of Cardiology, 4th Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China |
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Abstract: | We used patch-clamp techniques and A6 distal nephron cells as a model to determine how cholesterol regulates the renal epithelial
sodium channel (ENaC). We found that luminal methyl-β-cyclodextrin (mβCD, a cholesterol scavenger) did not acutely affect
ENaC activity at a previously used concentration of 10 mm but significantly decreased ENaC activity both when the cell membrane was stretched and at a higher concentration of 50 mm. Luminal cholesterol had no effect on ENaC activity at a concentration of 50 μg/ml but significantly increased ENaC activity
both when the cell membrane was stretched and at a higher concentration of 200 μg/ml. Confocal microscopy data indicate that
membrane tension facilitates both mβCD extraction of cholesterol and A6 cell uptake of exogenous cholesterol. Together with
previous findings that cholesterol in the apical membrane is tightly packed with sphingolipids and that stretch can affect
lipid distribution, our data suggest that membrane tension modulates the effects of mβCD and cholesterol on ENaC activity,
probably by facilitating both extraction and enrichment of apical cholesterol. |
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Keywords: | Patch-clamp technique Epithelial sodium channel Na+ transport Cholesterol Methyl-β -cyclodextrin Confocal microscopy NBD-cholesterol Renal epithelial cell |
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