文章基本信息

标题：Mechanism for attenuated outward conductance induced by mutations in the cytoplasmic pore of Kir2.1 channels
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作者：Hsueh-Kai Chang ; Masayuki Iwamoto ; Shigetoshi Oiki 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
DOI：10.1038/srep18404
出版社：Springer Nature
摘要：Outward currents through Kir2.1 channels regulate the electrical properties of excitable cells. These currents are subject to voltage-dependent attenuation by the binding of polyamines to high- and low-affinity sites, which leads to inward rectification, thereby controlling cell excitability. To examine the effects of positive charges at the low-affinity site in the cytoplasmic pore on inward rectification, we studied a mutant Kir channel (E224K/H226E) and measured single-channel currents and streaming potentials (V_stream), the latter provide the ratio of water to ions queued in a single-file permeation process in the selectivity filter. The water-ion coupling ratio was near one at a high K⁺ concentration ([K⁺]) for the wild-type channel and increased substantially as [K⁺] decreased. On the other hand, fewer ions occupied the selectivity filter in the mutant at all [K⁺]. A model for the Kir channel involving a K⁺ binding site in the wide pore was introduced. Model analyses revealed that the rate constants associated with the binding and release to and from the wide-pore K⁺ binding site was modified in the mutant. These effects lead to the reduced contribution of a conventional two-ion permeation mode to total conductance, especially at positive potentials, thereby inward rectification.