pH-Sensitive Kir Channel Antibody Explorer Kit

K_ir channels are comprised of two transmembrane segments and form tetramers where the P-domain and TM2 contribute to the permeation pore structure. The elementary conductance of all K_ir channels is dependent on extracellular K⁺ concentration over a large range. The subtypes K_ir1.1, K_ir4.X, K_ir5.1 and K_ir7.1 are involved in cell homeostasis and are sensitive to pH changes. K_ir1.1, K_ir4.1, and K_ir4.2 are inhibited by intracellular acidification with pK_a values of 6.5, 6.0, and 7.1, respectively.  The association of K_ir4.1 or K_ir4.2 with K_ir5.1 modifies the pK_a of the heterotetramers, making these channels highly sensitive to pH_i (K_ir4.1-K_ir5.1: 7.5; K_ir4.2/K_ir5.1: 7.6). At pH 7.3, a physiological pH, the open probability of K_ir1.1, K_ir4.1, and K_ir4.2 is nearly maximal. These homotetramers are sensitive to intracellular acidification than to alkalization. The open probability of the heterotetramers K_ir4.1/K_ir5.1 and K_ir4.2/K_ir5.1 is largely lower, around 0.3–0.4, implying high sensitivity to pH changes in both directions. K_ir7.1 exhibits a bell-shaped dependence on pH and appears rather insensitive to pH changes around pH 7.3.

K_ir1.1 (also known as ROMK) was extensively researched but currently the pH sensing mechanism of this channel remains unclear. Previous studies have shown that K_ir1.1 channels are closed by intracellular acidification with a pK_1/2 of 6.5, and the mechanism for this regulation is a trio of basic residues R41, K80, and R311. The K80 lysine residue was identified as the sensor itself but this hypothesis is being challenged by the idea that pH modulation takes place by an effect on an intrinsic gating mechanism common to all K_ir channels with pH sensitivity obeying the titration of a number of intracellular domain salt-bridges, stabilizing the channel in the open state¹.