Capillary K(+)-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow.

Capillary K(+)-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow.
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DOI:
10.1038/nn.4533
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发表时间:
2017-05
影响因子:
25
通讯作者:
Nelson MT
Nelson MT
中科院分区:
医学1区
文献类型:
--
作者:
Longden TA;Dabertrand F;Koide M;Gonzales AL;Tykocki NR;Brayden JE;Hill-Eubanks D;Nelson MT

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流入大脑的血液是动态调节的,以满足神经元不断变化的新陈代谢需求,但这是如何实现的仍不清楚。在这里,我们展示了毛细血管内皮细胞在感觉神经活动并以电血管扩张信号的形式将其传递到上游小动脉中的中心作用。我们进一步证明,这一信号是由神经活动的副产品细胞外钾(K+)启动的,它激活毛细血管内皮细胞内向整流钾(Kir2.1)通道,产生快速传播的逆行超极化,导致上游小动脉扩张,增加进入毛细血管床的血流量。我们的结果建立了大脑毛细血管作为一个活跃的感觉网络,将外部K+的变化转化为快速的、由内向外的电信号,将血液流动引导到活跃的大脑区域。
Blood flow into the brain is dynamically regulated to satisfy the changing metabolic requirements of neurons, but how this is accomplished has remained unclear. Here, we demonstrate a central role for capillary endothelial cells in sensing neural activity and communicating it to upstream arterioles in the form of an electrical vasodilatory signal. We further demonstrate that this signal is initiated by extracellular potassium (K+)—a byproduct of neural activity—which activates capillary endothelial cell inward-rectifier K+ (KIR2.1) channels to produce a rapidly propagating retrograde hyperpolarization that causes upstream arteriolar dilation, increasing blood flow into the capillary bed. Our results establish brain capillaries as an active sensory web that converts changes in external K+ into rapid, ‘inside-out’ electrical signaling to direct blood flow to active brain regions.