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

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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Makary SM,Claydon TW,Dibb KM,Boyett MR

doi

10.1529/biophysj.105.073569

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

4018-34

issue

11

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(06)72583-8

journal_volume

90

pub_type

杂志文章

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