Channelpedia

PubMed 12411513


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir2.1 , Kir2.2 , Kir2.3



Title: Identification of a site involved in the block by extracellular Mg(2+) and Ba(2+) as well as permeation of K(+) in the Kir2.1 K(+) channel.

Authors: Yoshimichi Murata, Yuichiro Fujiwara, Yoshihiro Kubo

Journal, date & volume: J. Physiol. (Lond.), 2002 Nov 1 , 544, 665-77

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12411513


Abstract
The inward rectifier potassium channel Kir2.1 is more sensitive to the weakly voltage-dependent block by extracellular Mg(2+) (Mg2+o) than Kir2.2 and Kir2.3. We identified Glu125 in an extracellular loop before the pore region of Kir2.1 as a site responsible for this sensitivity to M2+o block, based on the observations that the Glu125Gln (E125Q) mutation strongly decreased the sensitivity, while a mutation to Glu at the corresponding sites of Kir2.2 and 2.3 led to an increase. The negative charge proved to be crucial since the Glu125Asp (E125D) mutant showed similar properties to the wild type (WT). A similar weakly voltage-dependent block was also caused by extracellular Ca(2+) and La(3+) in Kir2.1 WT but not in the E125Q mutant. The sensitivity to block by extracellular Ba(2+) (Ba2+o) was also decreased in the E125Q mutant, although the voltage dependency of half-inhibition concentration was not changed, as reported previously. We additionally observed that the speed of Ba2+o block and recovery was decelerated by the presence of Mg2+o in WT, but not in the E125Q mutant. The sensitivity to the block by Mg2+o was increased by lowering extracellular K(+) (K+o), suggesting a competitive interaction of Mg2+o and K+o. The single-channel conductance of the WT in 140 mM K(+) was 39.6 pS (0 mM Mg2+o) and 11.5 pS (10 mM), while that of the E125Q mutant was 26.0 pS (0 mM) and 19.6 pS (10 mM). These results demonstrate that Mg(2+) competes with K(+) permeation in the WT and that E125 is required for efficient K(+) permeation in the absence of Mg2+o. We conclude that E125 in an extracellular loop of Kir2.1 is a site which facilitates K(+) permeation and entry of Ba(2+) toward a deeper plugging site, and that Mg2+o competes with K+o and Ba2+o at this site.