title: Extracellular links in Kir subunits control the unitary conductance of SUR/Kir6.0 ion channels.
abstract: Potassium (K+) channels are highly selective for K+ ions but their unitary conductances are quite divergent. Although Kir6.1 and Kir6.2 are highly homologous and both form functional K+ channels with sulfonylurea receptors, their unitary conductances measured with 150 mM extracellular K+ are approximately 35 and 80 pS, respectively. We found that a chain of three amino acid residues N123-V124-R125 of Kir6.1 and S113-I114-H115 of Kir6.2 in the M1-H5 extracellular link and single residues M148 of Kir6.1 and V138 of Kir6.2 in the H5-M2 link accounted for the difference. By using a 3D structure model of Kir6.2, we were able to recognize two independent plausible mechanisms involved in the determination of single channel conductance of the Kir6.0 subunits: (i) steric effects at Kir6.2V138 or Kir6.1M148 in the H5-M2 link influence directly the diffusion of K+ ions; and (ii) structural constraints between Kir6.2S113 or Kir6. 1N123 in the M1-H5 link and Kir6.2R136 or Kir6.1R146 near the H5 region control the conformation of the permeation pathway. These mechanisms represent a novel and possibly general aspect of the control of ion channel permeability.
authors.affiliation: Department of Pharmacology II, Faculty of Medicine and Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: V P
authors.initials: VP
authors.lastname: Repunte
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: A
authors.initials: A
authors.lastname: Fujita
authors.forename: Y
authors.initials: Y
authors.lastname: Horio
authors.forename: I
authors.initials: I
authors.lastname: Findlay
authors.forename: L
authors.initials: L
authors.lastname: Pott
authors.forename: Y
authors.initials: Y
authors.lastname: Kurachi
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D004553:Electric Conductivity; D006801:Humans; D006860:Hydrogen Bonding; D015640:Ion Channel Gating; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D016415:Sequence Alignment; D014162:Transfection
chemical_list: D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011993:Recombinant Fusion Proteins; D011188:Potassium