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Modulation of DEG/ENaCs by Amphiphiles Suggests Sensitivity to Membrane Alterations

Modulation of DEG/ENaCs by Amphiphiles Suggests Sensitivity to Membrane Alterations

Axel Schmidt, Rick J Alsop, Rahul Rimal, Pia Lenzig, Sylvia Joussen, Natalie N Gervasi, Adree Khondker, Stefan Gründer, Maikel C Rheinstädter, Dominik Wiemuth

Biophys J. 2018 Mar 27;114(6):1321-1335.

PMID: 29590590

Abstract:

The bile acid-sensitive ion channel is activated by amphiphilic substances such as bile acids or artificial detergents via membrane alterations; however, the mechanism of membrane sensitivity of the bile acid-sensitive ion channel is not known. It has also not been systematically investigated whether other members of the degenerin/epithelial Na+ channel (DEG/ENaC) gene family are affected by amphiphilic compounds. Here, we show that DEG/ENaCs ASIC1a, ASIC3, ENaC, and the purinergic receptor P2X2 are modulated by a large number of different, structurally unrelated amphiphilic substances, namely the detergents N-lauroylsarcosine, Triton X-100, and β-octylglucoside; the fenamate flufenamic acid; the antipsychotic drug chlorpromazine; the natural phenol resveratrol; the chili pepper compound capsaicin; the loop diuretic furosemide; and the antiarrythmic agent verapamil. We determined the modification of membrane properties using large-angle x-ray diffraction experiments on model lipid bilayers, revealing that the amphiphilic compounds are positioned in a characteristic fashion either in the lipid tail group region or in the lipid head group region, demonstrating that they perturbed the membrane structure. Collectively, our results show that DEG/ENaCs and structurally related P2X receptors are modulated by diverse amphiphilic molecules. Furthermore, they suggest alterations of membrane properties by amphiphilic compounds as a mechanism contributing to modulation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP4818591	Furosemide Related Compound A		4818-59-1	Price

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