title: Stoichiometry of Kir channels with phosphatidylinositol bisphosphate.
abstract: Phosphatidylinositol bisphosphate (PIP(2)) is the most abundant phosphoinositide in the plasma membrane of cells and its interaction with many ion channel proteins has proven to be a critical factor enabling ion channel gating. All members of the inwardly rectifying potassium (Kir) channel family depend on PIP(2) for their activity, displaying distinct affinities and stereospecificities of interaction with the phosphoinositide. Here, we explored the stoichiometry of Kir channels with PIP(2). We first showed that PIP(2) regulated the activity of Kir3.4 channels mainly by altering their bursting behavior. Detailed burst analysis indicates that the channels assumed up to four open states and a connectivity of four between open and closed states depending on the available PIP(2) levels. Moreover, by controlling the number of PIP(2)-sensitive subunits in the stoichiometry of a tetrameric Kir2.1 channel, we showed that characteristic channel activity was obtained when at least two wild-type subunits were present. Our studies support a kinetic model for gating of Kir channels by PIP(2), where each of the four open states corresponds to the channel activated by one to four PIP(2) molecules.
authors.affiliation: Department of Structural and Chemical Biology, Mount Sinai School of Medicine of New York University, New York, New York, USA.
authors.forename: Taihao
authors.initials: T
authors.lastname: Jin
authors.forename: Jin Liang
authors.initials: JL
authors.lastname: Sui
authors.forename: Avia
authors.initials: A
authors.lastname: Rosenhouse-Dantsker
authors.forename: Kim W
authors.initials: KW
authors.lastname: Chan
authors.forename: Lily Y
authors.initials: LY
authors.lastname: Jan
authors.forename: Diomedes E
authors.initials: DE
authors.lastname: Logothetis
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D015640:Ion Channel Gating; D007700:Kinetics; D008954:Models, Biological; D008956:Models, Chemical; D009154:Mutation; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry*; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry; D013997:Time Factors; D014981:Xenopus
chemical_list: D004791:Enzyme Inhibitors; C489461:Kir2.1 channel; D018129:Phosphatidylinositol Phosphates; D024661:Potassium Channels, Inwardly Rectifying