title: An extracellular ion pathway plays a central role in the cooperative gating of a K(2P) K+ channel by extracellular pH.
abstract: Proton-gated TASK-3 K(+) channel belongs to the K(2P) family of proteins that underlie the K(+) leak setting the membrane potential in all cells. TASK-3 is under cooperative gating control by extracellular [H(+)]. Use of recently solved K(2P) structures allows us to explore the molecular mechanism of TASK-3 cooperative pH gating. Tunnel-like side portals define an extracellular ion pathway to the selectivity filter. We use a combination of molecular modeling and functional assays to show that pH-sensing histidine residues and K(+) ions mutually interact electrostatically in the confines of the extracellular ion pathway. K(+) ions modulate the pK(a) of sensing histidine side chains whose charge states in turn determine the open/closed transition of the channel pore. Cooperativity, and therefore steep dependence of TASK-3 K(+) channel activity on extracellular pH, is dependent on an effect of the permeant ion on the channel pH(o) sensors.
authors: Centro de Estudios Científicos (CECs), 5110466 Valdivia, Chile.
authors: Wendy
authors: W
authors: González
authors: Leandro
authors: L
authors: Zúñiga
authors: L Pablo
authors: LP
authors: Cid
authors: Barbara
authors: B
authors: Arévalo
authors: María Isabel
authors: MI
authors: Niemeyer
authors: Francisco V
authors: FV
authors: Sepúlveda
mesh_terms: D000818:Animals; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology / Q000379:methods; D006168:Guinea Pigs; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating; D007477:Ions; D008564:Membrane Potentials; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D018408:Patch-Clamp Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000737:chemistry* / Q000378:metabolism; D011336:Probability; D011522:Protons; D055672:Static Electricity
chemical_list: D007477:Ions; C498655:KCNK9 protein, human; D024683:Potassium Channels, Tandem Pore Domain; D011522:Protons