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The second transmembrane domain of the large conductance, voltage‐ and calcium‐gated potassium channel β 1 subunit is a lithocholate sensor
Author(s) -
Bukiya An.,
Vaithianathan Thirumalini,
Toro Ligia,
Dopico Alejandro M.
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.01.036
Subject(s) - bk channel , calcium activated potassium channel , potassium channel , chemistry , protein subunit , heterologous expression , biophysics , sk channel , r type calcium channel , phosphatidylserine , n type calcium channel , ion channel , phosphatidylethanolamine , biochemistry , voltage dependent calcium channel , microbiology and biotechnology , phospholipid , calcium , biology , recombinant dna , t type calcium channel , membrane , phosphatidylcholine , receptor , organic chemistry , gene
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 β 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 β 1 to mediate LC action; β 1 and a simple phospholipid microenvironment suffice. Since β 1 senses LC but β 4 does not, we made chimeras swapping regions between these subunits and, following channel heterologous expression, demonstrate that β 1 TM2 is a bile acid‐recognizing sensor.