Local potassium signaling couples neuronal activity to vasodilation in the brain
Local potassium signaling couples neuronal activity to vasodilation in the brain
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DOI：
10.1038/nn1779
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发表时间：
2006-11-01
影响因子：
25
通讯作者：
Nelson, Mark T.
中科院分区：
文献类型：
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作者：
Filosa, Jessica A.;Bonev, Adrian D.;Nelson, Mark T.
活跃的神经元通过星形胶质细胞迅速向脑内小动脉发出扩张信号的机制仍不清楚。在此，我们发现，细胞外钾(K+)的适度升高激活了内向整流钾(KIR)通道，并引起了脑内小动脉平滑肌细胞(SMC)的膜电位超极化，而在大脑皮层脑片，KIR依赖的血管扩张和抑制SMC细胞内钙(Ca~(2+))的振荡。神经元激活引起快速(<；2 S潜伏期)血管扩张，这种作用可被KIR通道阻断大大减弱，并被同时抑制环氧合酶完全消除。星形细胞终足表现出大电导、钙敏感的K+(BK)通道电流，可被神经元刺激激活。阻断BK通道或阻断编码这些通道的基因可阻止神经诱导的血管扩张和小动脉SMC钙离子的抑制，但不影响星形胶质细胞钙离子的升高。这些结果支持了细胞间K+通道-K+通道信号的概念，星形细胞BK通道通过该信号对星形细胞钙信号形式的神经元活动进行解码，从而局部地将K+释放到血管周围间隙，激活SMC KIR通道，引起血管扩张。
The mechanisms by which active neurons, via astrocytes, rapidly signal intracerebral arterioles to dilate remain obscure. Here we show that modest elevation of extracellular potassium ( K+) activated inward rectifier K+ ( Kir) channels and caused membrane potential hyperpolarization in smooth muscle cells ( SMCs) of intracerebral arterioles and, in cortical brain slices, induced Kir-dependent vasodilation and suppression of SMC intracellular calcium ( Ca2+) oscillations. Neuronal activation induced a rapid ( < 2 s latency) vasodilation that was greatly reduced by Kir channel blockade and completely abrogated by concurrent cyclooxygenase inhibition. Astrocytic endfeet exhibited large-conductance, Ca2+-sensitive K+ ( BK) channel currents that could be activated by neuronal stimulation. Blocking BK channels or ablating the gene encoding these channels prevented neuronally induced vasodilation and suppression of arteriolar SMC Ca2+, without affecting the astrocytic Ca2+ elevation. These results support the concept of intercellular K+ channel-to-K+ channel signaling, through which neuronal activity in the form of an astrocytic Ca2+ signal is decoded by astrocytic BK channels, which locally release K+ into the perivascular space to activate SMC Kir channels and cause vasodilation.