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Updated: Apr 3, 2026

Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes
Published on: October 15, 2016
Molecular overlap in the regulation of SK channels by small molecules and phosphoinositides
Miao Zhang1, Xuan-Yu Meng2, Ji-Fang Zhang3
1Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, 1101 East Marshall Street, Richmond, VA 23298, USA ; Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, 9401 Jeronimo Road, Irvine, CA 92618, USA.
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.
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