The bile acid-sensitive ion channel (BASIC) is activated by alterations of its membrane environment

PLoS One. 2014 Oct 31;9(10):e111549. doi: 10.1371/journal.pone.0111549. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Sensing Ion Channels / chemistry
  • Acid Sensing Ion Channels / metabolism*
  • Animals
  • Bile Acids and Salts / pharmacology*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism*
  • Chlorpromazine / pharmacology
  • Cholesterol / pharmacology
  • Gadolinium / pharmacology
  • Ion Channel Gating / drug effects*
  • Mice
  • Picrates / pharmacology
  • Protein Structure, Tertiary
  • Rats
  • Structure-Activity Relationship
  • Ursodeoxycholic Acid / pharmacology
  • Xenopus laevis

Substances

  • Acid Sensing Ion Channels
  • Bile Acids and Salts
  • Picrates
  • Ursodeoxycholic Acid
  • Cholesterol
  • picric acid
  • Gadolinium
  • Chlorpromazine

Grants and funding

This study was supported by a grant of the Deutsche Forschungsgemeinschaft to DW (WI 4176/1-1). SDL is supported by Fundação para a Ciência e Tecnologia (SFRH/BPD/64265/2009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.