The bile acid-sensitive ion channel (BASIC) is activated by alterations of its membrane environment.
The bile acid-sensitive ion channel (BASIC) is activated by alterations of its membrane environment.
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DOI：
10.1371/journal.pone.0111549
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wiemuth D
中科院分区：
文献类型：
--
作者：
Schmidt A;Lenzig P;Oslender-Bujotzek A;Kusch J;Lucas SD;Gründer S;Wiemuth D
胆汁酸敏感离子通道(BASIC)是DEG/ENaC离子通道家族的成员。这一家族的通道具有共同的结构特征，但其生理功能和激活方式却多种多样。大鼠BASIC在脑、肝脏和肠道中表达，并被胆汁酸激活。碱性物质的生理功能及其激活胆汁酸的机制一直是个谜。在这里，我们解决了两亲胆汁酸是通过直接与通道结合还是通过改变周围膜的性质间接激活碱性的问题。我们发现，除胆汁酸以外的其他膜活性物质也影响碱性的活性，胆汁酸和其他膜活性物质的激活是非相加的，这表明碱性对其膜环境的变化是敏感的。此外，基于碱性和ASIC1a嵌合体的结果，我们表明细胞外和跨膜结构域对于膜敏感性是重要的。
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.
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