Extracellular links in Kir subunits control the unitary conductance of SUR/Kir6.0 ion channels.
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.
Repunte
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VP
Department of Pharmacology II, Faculty of Medicine and Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Nakamura
H
H
Fujita
A
A
Horio
Y
Y
Findlay
I
I
Pott
L
L
Kurachi
Y
Y
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
D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011993:Recombinant Fusion Proteins; D011188:Potassium