Base of pore loop is important for rectification, activation, permeation, and block of Kir3.1/Kir3.4

Biophysical Journal
Samy Y MakaryMark R Boyett

Abstract

The Kir3.1/Kir3.4 channel is an inward rectifier, agonist-activated K(+) channel. The location of the binding site within the channel pore that coordinates polyamines (and is thus responsible for inward rectification) and the location of the gate that opens the channel in response to agonist activation is unclear. In this study, we show, not surprisingly, that mutation of residues at the base of the selectivity filter in the pore loop and second transmembrane domain weakens Cs(+) block and decreases selectivity (as measured by Rb(+) and spermine permeation). However, unexpectedly, the mutations also weaken inward rectification and abolish agonist activation of the channel. In the wild-type channel and 34 mutant channels, there are significant (p < 0.05) correlations among the K(D) for Cs(+) block, Rb(+) and spermine permeation, inward rectification, and agonist activation. The significance of these findings is discussed. One possible conclusion is that the selectivity filter is responsible for inward rectification and agonist activation as well as permeation and block.

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Citations

Sep 20, 2006·Proceedings of the National Academy of Sciences of the United States of America·Delphine BichetLily Yeh Jan
Aug 26, 2009·Journal of Molecular and Cellular Cardiology·Justus M B Anumonwo, Anatoli N Lopatin
Jan 21, 2010·Physiological Reviews·Hiroshi HibinoYoshihisa Kurachi

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