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

Sci Rep. 2016 Feb 12;6:21493. doi: 10.1038/srep21493.


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 Mg(2+) on Kir2.1 channels is also closely correlated with K(+) current flow, and the coupled movements of Mg(2+) and K(+) seem to happen in the same flux-coupling segment of the pore as polyamines. With a preponderant outward K(+) flow, intracellular Mg(2+) 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 Mg(2+) does not seem to traverse the Kir2.1 channel pore in any case. Intracellular Mg(2+) 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 Mg(2+).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ion Transport / physiology
  • Magnesium / agonists
  • Magnesium / metabolism*
  • Mice
  • Potassium Channel Blockers / metabolism*
  • Potassium Channels, Inwardly Rectifying / antagonists & inhibitors*
  • Potassium Channels, Inwardly Rectifying / metabolism*
  • Spermine / agonists
  • Spermine / metabolism*
  • Xenopus laevis


  • Kir2.1 channel
  • Potassium Channel Blockers
  • Potassium Channels, Inwardly Rectifying
  • Spermine
  • Magnesium