In vivo stimulus-induced vasodilation occurs without IP3 receptor activation and may precede astrocytic calcium increase.
In vivo stimulus-induced vasodilation occurs without IP3 receptor activation and may precede astrocytic calcium increase.
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DOI：
10.1523/jneurosci.3285-12.2013
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发表时间：
2013-05-08
期刊：
影响因子：
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通讯作者：
Devor A
中科院分区：
文献类型：
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作者：
Nizar K;Uhlirova H;Tian P;Saisan PA;Cheng Q;Reznichenko L;Weldy KL;Steed TC;Sridhar VB;MacDonald CL;Cui J;Gratiy SL;Sakadzić S;Boas DA;Beka TI;Einevoll GT;Chen J;Masliah E;Dale AM;Silva GA;Devor A
血管活性胶质递质的钙依赖性释放被广泛认为触发与神经元活动快速增加相关的血管舒张。与这一假设不一致的是，在肌醇1，4，5-三磷酸（IP 3）2型受体（R2）敲除（KO）小鼠中观察到完整的刺激诱导的血管舒张，其中缺乏星形胶质细胞钙增加的主要机制-IP 3依赖性途径激活后从细胞内储存释放钙。此外，我们在野生型（WT）小鼠的结果表明，在体内发病的星形胶质细胞的钙增加响应于感觉刺激可以大大延迟相对于同时测量的发病的小动脉扩张。在WT小鼠中，在星形胶质细胞细胞体和血管周围终足中均观察到延迟的钙增加。因此，星形胶质细胞可能不会在血流反应的启动中发挥作用，至少不是通过钙依赖性机制。此外，在IP 3R 2-KO动物中，星形胶质细胞细胞内钙的增加对于正常的血管舒张是不需要的。
Calcium-dependent release of vasoactive gliotransmitters is widely assumed to trigger vasodilation associated with rapid increases in neuronal activity. Inconsistent with this hypothesis, intact stimulus-induced vasodilation was observed in inositol 1,4,5-triphosphate (IP3) type-2 receptor (R2) knockout (KO) mice, in which the primary mechanism of astrocytic calcium increase – the release of calcium from intracellular stores following activation of an IP3-dependent pathway – is lacking. Further, our results in wild type (WT) mice indicate that in vivo onset of astrocytic calcium increase in response to sensory stimulus could be considerably delayed relative to the simultaneously measured onset of arteriolar dilation. Delayed calcium increases in WT mice were observed in both astrocytic cell bodies and perivascular endfeet. Thus, astrocytes may not play a role in the initiation of blood flow response, at least not via calcium-dependent mechanisms. Moreover, an increase in astrocytic intracellular calcium was not required for normal vasodilation in the IP3R2-KO animals.