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

[摘要]

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⁺>NH₄ ⁺>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.

[学科分类] 生物化学/生物物理

[关键词] Inwardly rectifying K channel;Kir7.1;Kir2.1;Ion selectivity;Anomalous mole fraction;Multi-ion pore