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 T1(+) > K+ > Rb+ > NH4+ > Cs+ > Na+ > Li+, but the macroscopic conductance for Rb+ was similar to 8-fold larger than for the smaller K+ ions, and decreased similar to 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. (C) 2000 Federation of European Biochemical Societies.