AUTHOR=Zaydman Mark A. , Cui Jianmin 

TITLE=PIP2 regulation of KCNQ channels: biophysical and molecular mechanisms for lipid modulation of voltage-dependent gating

JOURNAL=Frontiers in Physiology

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2014.00195

DOI=10.3389/fphys.2014.00195

ISSN=1664-042X

ABSTRACT=<p>Voltage-gated potassium (Kv) channels contain voltage-sensing (VSD) and pore-gate (PGD) structural domains. During voltage-dependent gating, conformational changes in the two domains are coupled giving rise to voltage-dependent opening of the channel. In addition to membrane voltage, KCNQ (Kv7) channel opening requires the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP<sub>2</sub>). Recent studies suggest that PIP<sub>2</sub> serves as a cofactor to mediate VSD-PGD coupling in KCNQ1 channels. In this review, we put these findings in the context of the current understanding of voltage-dependent gating, lipid modulation of Kv channel activation, and PIP<sub>2</sub>-regulation of KCNQ channels. We suggest that lipid-mediated coupling of functional domains is a common mechanism among KCNQ channels that may be applicable to other Kv channels and membrane proteins.</p>