Molecular overlap in the regulation of SK channels by small molecules and phosphoinositides

Authors

Miao Zhang, Virginia Commonwealth University, Chapman University School of Pharmacy
Xuan-Yu Meng, Virginia Commonwealth UniversityFollow
Ji-fang Zhang, Thomas Jefferson University
Meng Cui, Virginia Commonwealth UniversityFollow
Diomedes E. Logothetis, Virginia Commonwealth UniversityFollow

Document Type

Article

Original Publication Date

2015

Journal/Book/Conference Title

Science Advances

Volume

1

Issue

6

DOI of Original Publication

10.1126/sciadv.1500008

Comments

Originally published at http://dx.doi.org/10.1126/sciadv.1500008

Date of Submission

December 2015

Abstract

Phosphatidylinositol 4,5-bisphosphate (PIP2) directly interacts with the small-conductance Ca2+-activated K+2-a (SK2-a) channel/calmodulin complex, serving as a critical element in the regulation of channel activity. We report that changes of protein conformation in close proximity to the PIP2 binding site induced by a small-molecule SK channel modulator, NS309, can effectively enhance the interaction between the protein and PIP2 to potentiate channel activity. This novel modulation of PIP2 sensitivity by small-molecule drugs is likely not to be limited in its application to SK channels, representing an intriguing strategy to develop drugs controlling the activity of the large number of PIP2-dependent proteins.

Rights

Copyright © 2015. The Authors This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

Is Part Of

VCU Physiology and Biophysics Publications