Kir4.1-mediated spatial buffering of K+: Experimental challenges in determination of its temporal and quantitative contribution to K+ clearance in the brain

Kir4.1-mediated spatial buffering of K+: Experimental challenges in determination of its temporal and quantitative contribution to K+ clearance in the brain
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DOI:
10.4161/19336950.2014.970448
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发表时间:
2014-11-01
期刊:
影响因子:
3.3
通讯作者:
MacAulay, Nanna
MacAulay, Nanna
中科院分区:
生物学3区
文献类型:
--
作者:
Larsen, Brian Roland;MacAulay, Nanna

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神经元活动导致 K+ 释放到中枢神经系统的细胞外空间。如果过量的 K+ 积累,神经元放电将因随后的神经元膜去极化而受到损害。周围的神经胶质细胞通过分子机制参与从细胞外间隙清除 K+,半个多世纪以来其身份一直存在争议。 Kir4.1 介导的 K+ 空间缓冲已被认为是 K+ 去除的主要贡献者,尽管其定量和时间贡献仍不确定。我们讨论了确定 Kir4.1 对神经元活动期间细胞外 K+ 管理的贡献所面临的生物物理和实验挑战。结论是:1) 实验制剂的几何形状对于检测 Kir4.1 介导的空间缓冲至关重要,2) Kir4.1 在神经元活动期间而非之后产生 K+ 空间缓冲。
Neuronal activity results in release of K+ into the extracellular space of the central nervous system. If the excess K+ is allowed to accumulate, neuronal firing will be compromised by the ensuing neuronal membrane depolarization. The surrounding glial cells are involved in clearing K+ from the extracellular space by molecular mechanism(s), the identity of which have been a matter of controversy for over half a century. Kir4.1-mediated spatial buffering of K+ has been promoted as a major contributor to K+ removal although its quantitative and temporal contribution has remained undefined. We discuss the biophysical and experimental challenges regarding determination of the contribution of Kir4.1 to extracellular K+ management during neuronal activity. It is concluded that 1) the geometry of the experimental preparation is crucial for detection of Kir4.1-mediated spatial buffering and 2) Kir4.1 enacts spatial buffering of K+ during but not after neuronal activity.