title: The bile acid-sensitive ion channel (BASIC) is activated by alterations of its membrane environment.
abstract: 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.
authors.affiliation: Institute of Physiology, RWTH Aachen University, Aachen, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Institute of Physiology, RWTH Aachen University, Aachen, Germany.
authors.forename: Pia
authors.initials: P
authors.lastname: Lenzig
authors.affiliation: Institute of Physiology, RWTH Aachen University, Aachen, Germany.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Oslender-Bujotzek
authors.affiliation: Institute of Physiology II, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Kusch
authors.affiliation: Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Susana Dias
authors.initials: SD
authors.lastname: Lucas
authors.affiliation: Institute of Physiology, RWTH Aachen University, Aachen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gründer
authors.affiliation: Institute of Physiology, RWTH Aachen University, Aachen, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Wiemuth
mesh_terms: D062565:Acid Sensing Ion Channels / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002746:Chlorpromazine / Q000494:pharmacology; D002784:Cholesterol / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D051379:Mice; D010851:Picrates / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D051381:Rats; D013329:Structure-Activity Relationship; D014580:Ursodeoxycholic Acid / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: D062565:Acid Sensing Ion Channels; D001647:Bile Acids and Salts; D010851:Picrates; D014580:Ursodeoxycholic Acid; D002784:Cholesterol; C005858:picric acid; D005682:Gadolinium; D002746:Chlorpromazine