Potassium buffering in the neurovascular unit: models and sensitivity analysis.
Potassium buffering in the neurovascular unit: models and sensitivity analysis.
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DOI：
10.1016/j.bpj.2013.09.012
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发表时间：
2013-11
影响因子：
3.4
通讯作者：
Alexandra Witthoft;J. Filosa;G. Karniadakis
中科院分区：
文献类型：
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作者：
Alexandra Witthoft;J. Filosa;G. Karniadakis
星形胶质细胞是神经和神经血管网络通信的关键调节器。钾转运是其许多功能背后的核心机制。星形胶质细胞用其远端突起包围突触，其表达两个钾泵（Na-K和NKCC）和一个内向整流钾通道（Kir），而邻近血管的终足表达Kir和BK钾通道。我们提供了一个详细的模型，钾流在整个神经血管单位（突触区，星形胶质细胞和小动脉）的皮层的年轻的大脑。我们的模型再现了实验观察到的几种现象：功能性充血，其中神经活动触发星形胶质细胞钾释放在血管周围endfoot，诱导小动脉扩张; K+下冲在神经活动期后的突触空间;神经诱导的星形胶质细胞超极化在Kir封锁。我们的研究结果表明，在功能性充血的血管反应的动力学是由星形胶质细胞Kir的快速发病和星形胶质细胞BK维持扩张。该模型支持K+下冲是由星形胶质细胞通过Na-K和NKCC泵的过度摄取引起的假设，而Kir平衡了该效应。我们使用高维随机敏感性分析解决参数的不确定性，并确定可能的模型限制。
Astrocytes are critical regulators of neural and neurovascular network communication. Potassium transport is a central mechanism behind their many functions. Astrocytes encircle synapses with their distal processes, which express two potassium pumps (Na-K and NKCC) and an inward rectifying potassium channel (Kir), whereas the vessel-adjacent endfeet express Kir and BK potassium channels. We provide a detailed model of potassium flow throughout the neurovascular unit (synaptic region, astrocytes, and arteriole) for the cortex of the young brain. Our model reproduces several phenomena observed experimentally: functional hyperemia, in which neural activity triggers astrocytic potassium release at the perivascular endfoot, inducing arteriole dilation; K+undershoot in the synaptic space after periods of neural activity; neurally induced astrocyte hyperpolarization during Kir blockade. Our results suggest that the dynamics of the vascular response during functional hyperemia are governed by astrocytic Kir for the fast onset and astrocytic BK for maintaining dilation. The model supports the hypothesis that K+undershoot is caused by excessive astrocytic uptake through Na-K and NKCC pumps, whereas the effect is balanced by Kir. We address parametric uncertainty using high-dimensional stochastic sensitivity analysis and identify possible model limitations.