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.
Highlights
The bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC family of ion channels [1]
Rat BASIC is modulated by chlorpromazine, trinitrophenol and gadolinium If bile acids activated rBASIC indirectly via their interaction with the lipid bilayer, we reasoned that other membrane active substances should affect the activity of the channel
To test the role of the plasma membrane for bile acid activation of rBASIC we applied TNP, CPZ and Gd3+ together with 2 mM of tauroursodeoxycholic acid (UDCA), which is found in rat bile [28] and strongly activates rBASIC (EC50: 2.5 mM) [14]
Summary
The bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC family of ion channels [1]. Based on the crystal structure of chicken acid-sensing ion channel (ASIC) 1 it is assumed that DEG/ENaC channels form homo- or heterotrimeric complexes and that the pore region is formed by the TMDs [3]. While the function of many DEG/ ENaC channels is known for some time, the physiological role of BASIC is still unknown. It is mainly expressed in hepatocytes and cholangiocytes of the liver, it is found in the intestinal tract and in the brain [4,5]. In humans its expression is restricted to the intestinal tract [7]
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