title: Determinant role of membrane helices in K ATP channel gating.
abstract: The ATP-sensitive K(+) (K(ATP)) channels couple chemical signals to cellular activity, in which the control of channel opening and closure (i.e., channel gating) is crucial. Transmembrane helices play an important role in channel gating. Here we report that the gating of Kir6.2, the core subunit of pancreatic and cardiac K(ATP) channels, can be switched by manipulating the interaction between two residues located in transmembrane domains (TM) 1 and 2 of the channel protein. The Kir6.2 channel is gated by ATP and proton, which inhibit and activate the channel, respectively. The channel gating involves two residues, namely, Thr71 and Cys166, located at the interface of the TM1 and TM2. Creation of electrostatic attraction between these sites reverses the channel gating, which makes the ATP an activator and proton an inhibitor of the channel. Electrostatic repulsion with two acidic residues retains or even enhances the wild-type channel gating. A similar switch of the pH-dependent channel gating was observed in the Kir2.1 channel, which is normally pH- insensitive. Thus, the manner in which the TM1 and TM2 helices interact appears to determine whether the channels are open or closed following ligand binding.
authors: Department of Biology, Georgia State University, 24 Peachtree Center Avenue, Atlanta, GA 30303-4010, USA.
authors: R
authors: R
authors: Wang
authors: A
authors: A
authors: Rojas
authors: J
authors: J
authors: Wu
authors: H
authors: H
authors: Piao
authors: C Y
authors: CY
authors: Adams
authors: H
authors: H
authors: Xu
authors: Y
authors: Y
authors: Shi
authors: Y
authors: Y
authors: Wang
authors: C
authors: C
authors: Jiang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D020134:Catalytic Domain / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000235:genetics / Q000502:physiology*; D008564:Membrane Potentials / Q000235:genetics / Q000502:physiology; D009865:Oocytes / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary / Q000235:genetics / Q000502:physiology; D011522:Protons; D014162:Transfection; D014982:Xenopus laevis; D000099161:Kcnj11 Channel
chemical_list: D000255:Adenosine Triphosphate; D024661:Potassium Channels, Inwardly Rectifying; D011522:Protons; D000099161:Kcnj11 Channel; C489457:KCNJ2 protein, human