A synergistic blocking effect of Mg²⁺ and spermine on the inward rectifier K⁺ (Kir2.1) channel pore.

Abstract

Inward rectifier K+ channels (Kir2.1) exhibit an extraordinary rectifying feature in the current–voltage relationship. We have previously showed that the bundle–crossing region of the transmembrane domain constitutes the crucial segment responsible for the polyamine block. In this study, we demonstrated that the major blocking effect of intracellular Mg2+ on Kir2.1 channels is also closely correlated with K+ current flow, and the coupled movements of Mg2+ and K+ seem to happen in the same flux–coupling segment of the pore as polyamines. With a preponderant outward K+ flow, intracellular Mg2+ would also be pushed to and thus stay at the outermost site of a flux–coupling segment in the bundle–crossing region of Kir2.1 channels to block the pore, although with a much lower apparent affinity than spermine (SPM). However, in contrast to the evident possibilities of outward exit of SPM through the channel pore especially during strong membrane depolarization, intracellular Mg2+ does not seem to traverse the Kir2.1 channel pore in any case. Intracellular Mg2+ and SPM therefore may have a synergistic action on the pore–blocking effect, presumably via prohibition of the outward exit of the higher–affinity blocking SPM by the lower–affinity Mg2+.