Stable cation coordination at a single outer pore residue defines permeation properties in Kir channels

• Published in: FEBS letters 2000-01, Vol.466 (1), p.115-120
• Main Authors: Wischmeyer, Erhard, Döring, Frank, Karschin, Andreas
• Format: Article
• Language: English
• Subjects: Animals; Anomalous mole fraction; Binding Sites - genetics; Female; Humans; In Vitro Techniques; Inwardly rectifying K channel; Ion selectivity; Kir2.1; Kir7.1; Membrane Potentials; Multi-ion pore; Mutagenesis, Site-Directed; Oocytes - metabolism; Permeability; Potassium - metabolism; Potassium Channels - chemistry; Potassium Channels - genetics; Potassium Channels - metabolism; Potassium Channels, Inwardly Rectifying; Rats; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Xenopus laevis
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(99)01769-X

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 ∼8-fold larger than for the smaller K + ions, and decreased ∼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.