A conserved arginine near the filter of Kir1.1 controls Rb/K selectivity.

ABSTRACT: ROMK (Kir1.1) channels are important for K secretion and recycling in the collecting duct, connecting tubule and thick ascending limb of the mammalian nephron. We have identified a highly conserved Arg in the P loop of the channel near the selectivity filter that controls Rb/K selectivity. Mutation of this Arg to a Tyr (R128Y-Kir1.1b, R147Y-Kir1.1a) increased the macroscopic conductance ratio, G(Rb)/G(K) by 17 ± 3 fold and altered the selectivity sequence from NH(4) > K > Tl > Rb >> Cs in wt-Kir1.1 to: Rb > Cs > Tl > NH(4) >> K in R128Y, without significant change in the high K/Na permeability ratio of Kir1.1. R128M produced similar, but smaller, increases in Rb, Tl, NH(4) and Cs conductance relative to K. R128Y remained susceptible to block by both external Ba and the honeybee toxin, TPNQ

SUBMITTER: Sackin H 

PROVIDER: S-EPMC2935938 | biostudies-literature | 2010 May-Jun

REPOSITORIES: biostudies-literature