title: Phosphatidylinositol (4,5)-bisphosphate dynamically regulates the K2Pbackground K+channel TASK-2.
abstract: Two-pore domain K2PK+channels responsible for the background K+conductance and the resting membrane potential, are also finely regulated by a variety of chemical, physical and physiological stimuli. Hormones and transmitters acting through Gq protein-coupled receptors (GqPCRs) modulate the activity of various K2Pchannels but the signalling involved has remained elusive, in particular whether dynamic regulation by membrane PI(4,5)P2, common among other classes of K+channels, affects K2Pchannels is controversial. Here we show that K2PK+channel TASK-2 requires PI(4,5)P2for activity, a dependence that accounts for its run down in the absence of intracellular ATP and its full recovery by addition of exogenous PI(4,5)P2, its inhibition by low concentrations of polycation PI scavengers, and inhibition by PI(4,5)P2depletion from the membrane. Comprehensive mutagenesis suggests that PI(4,5)P2interaction with TASK-2 takes place at C-terminus where three basic aminoacids are identified as being part of a putative binding site.
authors.affiliation: Centro de Estudios Científicos (CECs), Avenida Arturo Prat 514, Valdivia, Chile.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Niemeyer
authors.affiliation: Centro de Estudios Científicos (CECs), Avenida Arturo Prat 514, Valdivia, Chile.
authors.forename: L Pablo
authors.initials: LP
authors.lastname: Cid
authors.affiliation: UPMC Université Paris 06, UMR_S 1138, Team 3 and INSERM, UMR_S 872, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Paulais
authors.affiliation: UPMC Université Paris 06, UMR_S 1138, Team 3 and INSERM, UMR_S 872, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Teulon
authors.affiliation: Centro de Estudios Científicos (CECs), Avenida Arturo Prat 514, Valdivia, Chile.
authors.forename: Francisco V
authors.initials: FV
authors.lastname: Sepúlveda
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004075:Diglycerides / Q000494:pharmacology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009355:Neomycin / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism
chemical_list: D004075:Diglycerides; C498739:Kcnk5 protein, mouse; D019269:Phosphatidylinositol 4,5-Diphosphate; D024683:Potassium Channels, Tandem Pore Domain; D021122:Protein Subunits; D000255:Adenosine Triphosphate; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D009355:Neomycin