The second transmembrane domain of the large conductance, voltage‐ and calcium‐gated potassium channel β1 subunit is a lithocholate sensor
Open Access
- 31 January 2008
- journal article
- research article
- Published by Wiley in FEBS Letters
- Vol. 582 (5), 673-678
- https://doi.org/10.1016/j.febslet.2008.01.036
Abstract
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.Keywords
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