Stable cation coordination at a single outer pore residue defines permeation properties in Kir channels.
In epithelial Kir7.1 channels a non-conserved methionine in the outer pore region adjacent to the G-Y-G selectivity filter (position +2) was found to determine unique properties for permeant and blocking ions characteristic of a K(+) channel in a single-occupancy state. The monovalent cation permeability sequence of Kir7.1 channels expressed in Xenopus oocytes was Tl(+)>K(+)>Rb(+)NH(4)(+)>Cs(+)>Na(+)>Li(+), but the macroscopic conductance for Rb(+) was approximately 8-fold larger than for the smaller K(+) ions, and decreased approximately 40-fold with the conserved arginine at the +2 position (Kir7.1M125R). Moreover, in Kir7.1 Rb(+) restored the typical permeation properties of other multi-ion channels indicating that a stable coordination of permeant ions at the +2 position defines the initial step in the conduction pathway of Kir channels.
Wischmeyer
E
E
Department of Molecular Neurobiology of Signal Transduction, Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, 37070, Göttingen, Germany.
Döring
F
F
Karschin
A
A
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000378:metabolism; D010539:Permeability; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis
D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011994:Recombinant Proteins; D011188:Potassium