期刊
FEBS LETTERS
卷 582, 期 5, 页码 673-678出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2008.01.036
关键词
maxiK channel; KCNMB1; lithocholic acid; bile acids; steroids
资金
- NHLBI NIH HHS [R01 HL077424-04, HL 54970, R01 HL077424, HL 77424, R01 HL054970] Funding Source: Medline
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 beta(1) 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 beta(1), to mediate LC action; beta(1)and a simple phospholipid microenvironment suffice. Since beta(1) senses LC but beta(4) does not, we made chimeras swapping regions between these subunits and, following channel heterologous expression, demonstrate that beta(1) TM2 is a bile acid-recognizing sensor. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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