Dual Effect of Phosphatidyl (4,5)-Bisphosphate PIP2on Shaker K+Channels

Abderemane-Ali F, Es-Salah-Lamoureux Z, Delemotte L, Kasimova MA, Labro AJ, Snyders DJ, Fedida D, Tarek M, BarĂ³ I, Loussouarn G

J. Biol. Chem. 287 (43) 36158-36167 [2012-10-19; online 2012-08-29]

Phosphatidylinositol (4,5)-bisphosphate (PIP(2)) is a phospholipid of the plasma membrane that has been shown to be a key regulator of several ion channels. Functional studies and more recently structural studies of Kir channels have revealed the major impact of PIP(2) on the open state stabilization. A similar effect of PIP(2) on the delayed rectifiers Kv7.1 and Kv11.1, two voltage-gated K(+) channels, has been suggested, but the molecular mechanism remains elusive and nothing is known on PIP(2) effect on other Kv such as those of the Shaker family. By combining giant-patch ionic and gating current recordings in COS-7 cells, and voltage-clamp fluorimetry in Xenopus oocytes, both heterologously expressing the voltage-dependent Shaker channel, we show that PIP(2) exerts 1) a gain-of-function effect on the maximal current amplitude, consistent with a stabilization of the open state and 2) a loss-of-function effect by positive-shifting the activation voltage dependence, most likely through a direct effect on the voltage sensor movement, as illustrated by molecular dynamics simulations.

Lucie Delemotte

SciLifeLab Fellow

PubMed 22932893

DOI 10.1074/jbc.m112.382085

Crossref 10.1074/jbc.m112.382085

Publications 9.5.0