Open AccessThe Bile Acid-Sensitive Ion Channel (BASIC) Is Activated by Alterations of Its Membrane Environment
Author(s) -
Axel Schmidt,
Pia Lenzig,
Adrienne Oslender-Bujotzek,
Jana Kusch,
Susana D. Lucas,
Stefan Gründer,
Dominik Wiemuth
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0111549
Subject(s) - bile acid , ion channel , transmembrane protein , membrane , extracellular , biochemistry , biophysics , chemistry , transmembrane channels , amino acid , membrane protein , biology , microbiology and biotechnology , voltage gated ion channel , receptor
The bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC family of ion channels. Channels of this family are characterized by a common structure, their physiological functions and modes of activation, however, are diverse. Rat BASIC is expressed in brain, liver and intestinal tract and activated by bile acids. The physiological function of BASIC and its mechanism of bile acid activation remain a puzzle. Here we addressed the question whether amphiphilic bile acids activate BASIC by directly binding to the channel or indirectly by altering the properties of the surrounding membrane. We show that membrane-active substances other than bile acids also affect the activity of BASIC and that activation by bile acids and other membrane-active substances is non-additive, suggesting that BASIC is sensitive for changes in its membrane environment. Furthermore based on results from chimeras between BASIC and ASIC1a, we show that the extracellular and the transmembrane domains are important for membrane sensitivity.