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Mechanism of Ba 2+ block of a mouse inwardly rectifying K + channel: differential contribution by two discrete residues
Author(s) -
Alagem Noga,
Dvir Miri,
Reuveny Eitan
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.00381.x
Subject(s) - chemistry , xenopus , biophysics , alanine , asparagine , kinetics , ion , amino acid , potassium channel , stereochemistry , biochemistry , biology , physics , organic chemistry , quantum mechanics , gene
1 The block of the IRK1/Kir2.1 inwardly rectifying K + channel by a Ba 2+ ion is highly voltage dependent, where the ion binds approximately half‐way within the membrane electrical field. The mechanism by which two distinct mutations, E125N and T141A, affect Ba 2+ block of Kir2.1 was investigated using heterologous expression in Xenopus oocytes. 2 Analysis of the blocking kinetics showed that E125 and T141 affect the entry and binding of Ba 2+ to the channel, respectively. Replacing the glutamate at position 125 with an asparagine greatly decreased the rate at which the Ba 2+ ions enter and leave the pore. In contrast, replacing the polar threonine at position 141 with an alanine affected the entry rate of the Ba 2+ ions while leaving the exit rate unchanged. 3 Acidification of the extracellular solution slowed the exit rate of the Ba 2+ from the wild‐type channel, but had no such effect on the Kir2.1(E125N) mutant. 4 These results thus reveal two unique roles for the amino acids at positions 125 and 141 in aiding the interaction of Ba 2+ with the channel. Their possible roles in K + permeation are discussed.