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在关键去极化时激活电压敏感离子通道的分子步骤。

On molecular steps that activate a voltage sensitive ion channel at critical depolarization.

机构信息

Texas Southern University, Houston, TX, USA.

出版信息

Biophys Chem. 2023 Oct;301:107078. doi: 10.1016/j.bpc.2023.107078. Epub 2023 Jul 26.

DOI:10.1016/j.bpc.2023.107078
PMID:37544083
Abstract

At high transmembrane electric field, a voltage sensitive ion channel is an insulator; when the field is critically reduced, it becomes a conductor of selected ions. The Channel Activation by Electrostatic Repulsion (CAbER) hypothesis proposes that an ordered polarization field of induced dipoles at the high electric field magnitude of the excitable state is overcome by thermal disorder at a critical depolarization. Increased repulsions between positive charges in the S4 segments cause an allosteric transition in which these segments expand and separate in a chiral proteinquake. The increased space allows the P segments to refold and the ion-semiconducting S5 and S6 segments to relax and expand outward in a breathing mode. Stripped permeant ions enter widened hydrogen bonds in the core helices of these segments. Driven by concentration differences and the electric field, the ions hop along transient pathways across the channel, appearing as fractal, stochastic bursts of single-channel currents. To support order amid thermal fluctuations, an object must be of a minimum size. The critical role of an ion channel's size suggests that the evolution of Metazoa became possible only after its DNA had grown enough to code for proteins larger than the correlation length.

摘要

在高跨膜电场下,电压敏感离子通道是一种绝缘体;当电场临界降低时,它变成了选定离子的导体。静电排斥致通道激活(CAbER)假说提出,在兴奋状态的高电场强度下,感应偶极子的有序极化场被临界去极化的热无序所克服。S4 片段中带正电荷的斥力增加导致变构转变,这些片段在手性蛋白地震中展开并分离。空间的增加允许 P 片段重新折叠,离子半导体 S5 和 S6 片段以呼吸模式向外松弛和扩张。穿透性离子进入这些片段核心螺旋中的加宽氢键。在浓度差和电场的驱动下,离子沿着瞬态途径在通道中跳跃,表现为分形、随机的单通道电流爆发。为了在热波动中保持有序,物体必须具有最小尺寸。离子通道大小的关键作用表明,后生动物的进化只有在其 DNA 足够长以编码大于相关长度的蛋白质后才成为可能。

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