Calcium transients in astrocyte endfeet cause cerebrovascular constrictions
Calcium transients in astrocyte endfeet cause cerebrovascular constrictions
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DOI：
10.1038/nature02827
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发表时间：
2004-09-09
期刊：
影响因子：
64.8
通讯作者：
MacVicar, BA
中科院分区：
文献类型：
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作者：
Mulligan, SJ;MacVicar, BA
脑血流量(CBF)与神经元活动相关联，并在体内成像以绘制大脑激活图(1)。CBF还受到传入投射纤维的调节，这些纤维在血管周围区域释放血管活性神经递质(2，3)，主要是在勾勒脑血管(6)的星形胶质细胞末端足部(4，5)。然而，星形胶质细胞在脑血管张力调节中的作用仍不确定。在这里，我们用双光子钙离子注入(7，8)来增加[Ca~(2+)](I)，以确定星形胶质细胞内钙离子浓度([Ca~(2+)](I))对小动脉直径的影响。血管收缩发生在由去钙引起的钙波进入星形胶质细胞末端足部并引起[Ca~(2+)](I)的大幅升高时。血管活性神经递质去甲肾上腺素(2，3)使星形胶质细胞终足[Ca~(2+)](I)升高，峰值出现在小动脉收缩之前。用BAPTA抑制星形胶质细胞[Ca~(2+)](I)升高，可抑制去甲肾上腺素的血管收缩作用。我们发现，星形胶质细胞终足[Ca~(2+)](I)升高引起的脑血管收缩是通过磷脂酶A(2)-花生四烯酸途径和20-羟基二十碳四烯酸的产生而产生的。星形胶质细胞收缩血管是一种先前未知的调节CBF的机制。
Cerebral blood flow (CBF) is coupled to neuronal activity and is imaged in vivo to map brain activation(1). CBF is also modified by afferent projection fibres that release vasoactive neurotransmitters(2,3) in the perivascular region, principally on the astrocyte endfeet(4,5) that outline cerebral blood vessels(6). However, the role of astrocytes in the regulation of cerebrovascular tone remains uncertain. Here we determine the impact of intracellular Ca2+ concentrations ([Ca2+](i)) in astrocytes on the diameter of small arterioles by using two-photon Ca2+ uncaging(7,8) to increase [Ca2+](i). Vascular constrictions occurred when Ca2+ waves evoked by uncaging propagated into the astrocyte endfeet and caused large increases in [Ca2+](i). The vasoactive neurotransmitter noradrenaline(2,3) increased [Ca2+](i) in the astrocyte endfeet, the peak of which preceded the onset of arteriole constriction. Depressing increases in astrocyte [Ca2+](i) with BAPTA inhibited the vascular constrictions in noradrenaline. We find that constrictions induced in the cerebrovasculature by increased [Ca2+](i) in astrocyte endfeet are generated through the phospholipase A(2)-arachidonic acid pathway and 20-hydroxyeicosatetraenoic acid production. Vasoconstriction by astrocytes is a previously unknown mechanism for the regulation of CBF.