title: 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 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+).
authors: Department of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Chiung-Wei
authors: CW
authors: Huang
authors: Department of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
authors: Chung-Chin
authors: CC
authors: Kuo
mesh_terms: D000818:Animals; D017136:Ion Transport / Q000502:physiology; D008274:Magnesium / Q000819:agonists / Q000378:metabolism*; D051379:Mice; D026902:Potassium Channel Blockers / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013096:Spermine / Q000819:agonists / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: C489461:Kir2.1 channel; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D013096:Spermine; D008274:Magnesium