title: Dual effect of phosphatidylinositol (4,5)-bisphosphate PIP(2) on Shaker K(+) [corrected] channels.
abstract: 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.
authors.affiliation: INSERM, UMR 1087, Nantes, F-44007, France.
authors.forename: Fayal
authors.initials: F
authors.lastname: Abderemane-Ali
authors.forename: Zeineb
authors.initials: Z
authors.lastname: Es-Salah-Lamoureux
authors.forename: Lucie
authors.initials: L
authors.lastname: Delemotte
authors.forename: Marina A
authors.initials: MA
authors.lastname: Kasimova
authors.forename: Alain J
authors.initials: AJ
authors.lastname: Labro
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Snyders
authors.forename: David
authors.initials: D
authors.lastname: Fedida
authors.forename: Mounir
authors.initials: M
authors.lastname: Tarek
authors.forename: Isabelle
authors.initials: I
authors.lastname: Baró
authors.forename: Gildas
authors.initials: G
authors.lastname: Loussouarn
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D015640:Ion Channel Gating / Q000502:physiology*; D051657:KCNQ1 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000235:genetics / Q000378:metabolism*; D051637:Shaker Superfamily of Potassium Channels / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus
chemical_list: D051657:KCNQ1 Potassium Channel; D019269:Phosphatidylinositol 4,5-Diphosphate; D051637:Shaker Superfamily of Potassium Channels