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.
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