Premium
Extracellular links in Kir subunits control the unitary conductance of SUR/Kir6.0 ion channels
Author(s) -
Repunte Vez P.,
Nakamura Haruki,
Fujita Akikazu,
Horio Yoshiyuki,
Findlay Ian,
Pott Lutz,
Kurachi Yoshihisa
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.12.3317
Subject(s) - biology , extracellular , conductance , ion channel , protein subunit , biophysics , microbiology and biotechnology , biochemistry , genetics , physics , gene , condensed matter physics , receptor
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 ∼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.