The second transmembrane domain of the large conductance, voltage- and calcium-gated potassium channel β₁ subunit is a lithocholate sensor

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• 作者：Anna N. Bukiya ; Thirumalini Vaithianathan ; Ligia Toro ; Alej ; ro M. Dopico
• 关键词：MaxiK channel ; KCNMB1 ; Lithocholic acid ; Bile acids ; Steroids
• 刊名：FEBS Letters
• 出版年：2008
• 出版时间：5 March 2008
• 年：2008
• 卷：582
• 期：5
• 页码：673-678
• 全文大小：1397 K

文摘

Bile acids and other steroids modify large conductance, calcium- and voltage-gated potassium (BK) channel activity contributing to non-genomic modulation of myogenic tone. Accessory BK β₁ subunits are necessary for lithocholate (LC) to activate BK channels and vasodilate. The protein regions that sense steroid action, however, remain unknown. Using recombinant channels in 1-palmitoyl-2-oleoyl-phosphatidylethanolamine/1-palmitoyl-2-oleoyl-phosphatidylserine bilayers we now demonstrate that complex proteolipid domains and cytoarchitecture are unnecessary for β₁ to mediate LC action; β₁ and a simple phospholipid microenvironment suffice. Since β₁ senses LC but β₄ does not, we made chimeras swapping regions between these subunits and, following channel heterologous expression, demonstrate that β₁ TM2 is a bile acid-recognizing sensor.