Molecular overlap in the regulation of SK channels by small molecules and phosphoinositides.
basic_science · Level V
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- Record sourced from PubMed, PMID 26366439.
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Abstract
Phosphatidylinositol 4,5-bisphosphate (PIP<sub>2</sub>) directly interacts with the small-conductance Ca<sup>2+</sup>-activated K<sup>+</sup> 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 PIP<sub>2</sub> binding site induced by a small-molecule SK channel modulator, NS309, can effectively enhance the interaction between the protein and PIP<sub>2</sub> to potentiate channel activity. This novel modulation of PIP<sub>2</sub> 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 PIP<sub>2</sub>-dependent proteins.