FEBS Letters
Volume 582, Issue 5 , Pages 673-678, 5 March 2008

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

Edited by Robert Barouki

  • Anna N. Bukiya

      Affiliations

    • Department of Pharmacology, University of Tennessee HSC, Memphis, TN 38163, United States
    • ,
  • Thirumalini Vaithianathan

      Affiliations

    • Department of Pharmacology, University of Tennessee HSC, Memphis, TN 38163, United States
    • ,
  • Ligia Toro

      Affiliations

    • Department of Anesthesiology, University of California at Los Angeles, Los Angeles, CA 90095, United States
    • ,
  • Alejandro M. Dopico

      Affiliations

    • Department of Pharmacology, University of Tennessee HSC, Memphis, TN 38163, United States
    • Corresponding Author InformationCorresponding author. Fax: +1 901 448 1695.

Received 7 December 2007; received in revised form 17 January 2008; accepted 23 January 2008. published online 31 January 2008.

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 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.

Abbreviations: LC, lithocholate, BK, large conductance, calcium- and voltage-gated potassium, POPE, 1-palmitoyl-2-oleoyl-phosphatidylethanolamine, POPS, 1-palmitoyl-2-oleoyl-phosphatidylserine, DMSO, dimethyl sulfoxide (DMSO), N, number of channels present in the membrane patch/lipid bilayer, Po, channel open probability, Ibtx, iberiotoxin

Keywords: MaxiK channel, KCNMB1, Lithocholic acid, Bile acids, Steroids

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PII: S0014-5793(08)00063-X

doi:10.1016/j.febslet.2008.01.036

FEBS Letters
Volume 582, Issue 5 , Pages 673-678, 5 March 2008

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