K+ Binding Sites and Interactions between Permeating K+ Ions at the External Pore Mouth of an Inward Rectifier K+ Channel (Kir2.1)

Kir2.3 isoform confers pH sensitivity to heteromeric Kir2.1/Kir2.3 channels in HEK293 cells

“…We assumed that homomeric Kir2.1 single channels are insensitive to pH challenges in the range we have studied (5.0 to 9.0). This assumption is supported by previous studies that demonstrate insensitivity to pH of single channels at this same range of values [25].…”

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

“…Kubo [11] first reported slowing of current activation and a negative shift of the I/V relationship in Kir2.1R148Y mutants reasoning that this site was involved in the interaction with K + , gating and block of Kir2.1. In the following it was demonstrated that this site, which is just outside the membrane electrical field, was accessible to external H + , and acts as an external barrier for divalent cations such as Mg 2+ [12,13]. Using Kir7.1 channels which naturally harbor a methionine residue at the +2 position we provide evidence in this report that this site acts as a K + /Rb + switch, is crucially involved in the stable coordination and permeation of monovalent ions, and defines the initial step in the conduction pathway of the pore.…”

Polyamine Permeation and Rectification of Kir4.1 Channels

“…30 Recent models are still consistent with this general idea, and multiple mutagenesis studies have indicated that the shallow site is associated with the cytoplasmic vestibule of the Kir channel, whereas the deep site is in the inner cavity or the entrance to the selectivity filter. 21,22,29,[31][32][33][34] In such a model, it is easy to see how shallow binding may not completely occlude the channel 35,36 but it is difficult to imagine that significant K + permeation could occur when the polyamine is bound at a deep site in the inner cavity. A small pedestal of non-blocked current at positive voltages and very low (< 1 mM) spermine or spermidine concentrations has been reported previously for Kir2.1, 32 leading to the proposal that there is a finite rate of polyamine permeation through the selectivity filter.…”