About this item:

247 Views | 598 Downloads

Author Notes:

Address correspondence to: Douglas C. Eaton, Emory University School of Medicine, Department of Physiology, Whitehead Biomedical Research Building, 615 Michael Street, Atlanta, GA 30322, Phone: 001-(404) 727-7421, Fax: 001-(404) 727-0329, deaton@emory.edu.

Unoprostone is a product of Sucampo.

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.


Research Funding:

This work was supported by a grant from Sucampo Pharmaceuticals, LLC, and NIH DK R37DK037963 to DCE.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Biophysics
  • BK channels
  • KCNMA1
  • Unoprostone
  • Rescula (R)
  • Single channels
  • Ca2+-dependence
  • GH(3) CELLS
  • FP

Unoprostone activation of BK (K(ca)1.1) channel splice variants


Journal Title:

Biochimica et Biophysica Acta - Biomembranes


Volume 1848, Number 11


, Pages 2859-2867

Type of Work:

Article | Post-print: After Peer Review


This investigation was conducted to study the relationship between intracellular Ca2+ and activation of large conductance Ca2+-activated K+ (BK) currents by unoprostone, the first synthetic docosanoid. We used HEK293 cells stably transfected with two BK channel splice variants, one sensitive to unoprostone and the other insensitive. We examined the effects of unoprostone on channel activity in excised inside-out patches and cell-attached patches. The half-maximal stimulation of the sensitive BK channels by Ca2+ was shifted from 3.4 ± 0.017 nM to 0.81 ± .0058 nM in the presence of 10 nM unoprostone. There was no effect on insensitive channels even at unoprostone concentrations as high as 1000 nM. There was no effect of unoprostone on the voltage dependence of the BK channels. Changes in open probability and effects of Ca2+ and unoprostone were best described by a synergistic binding model. These data would suggest that Ca2+ and unoprostone were binding to sites close to one another on the channel protein and that unoprostone binding causes the affinity of the calcium binding site to increase. This idea is consistent with three dimensional models of the Ca2+ binding site and a putative unoprostone binding domain. Our results have important implications for the clinical use of unoprostone to activate BK channels. Channel activation will be limited if intracellular Ca2+ is not elevated.

Copyright information:

© 2015 Elsevier B.V.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Creative Commons License

Export to EndNote