Ectopic vesicular neurotransmitter release along sensory axons mediates neurovascular coupling via glial calcium signaling
Ectopic vesicular neurotransmitter release along sensory axons mediates neurovascular coupling via glial calcium signaling
复制标题
异位囊泡神经递质沿感觉轴突释放通过神经胶质钙信号传导介导神经血管耦合
DOI：
10.1073/pnas.1003501107
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
C. Lohr
中科院分区：
文献类型：
--
作者：
A. Thyssen;Daniela Hirnet;H. Wolburg;G. Schmalzing;J. Deitmer;C. Lohr
神经递质的释放通常被认为发生在突触的活动区，并且在少数情况下已经证明了神经递质的异位释放。然而，异位神经递质释放的机制知之甚少。我们利用嗅觉受体轴突和专门的胶质细胞、嗅鞘细胞（OECs）在形态和功能上的密切接近来研究异位神经递质释放。轴突刺激诱发嘌呤能和谷氨酸能的Ca 2+反应，表明ATP和谷氨酸的释放。在表达突触-pHluorin的轴突中，刺激引起突触-pHluorin荧光的增加，指示囊泡融合。神经递质的释放依赖于Ca ~（2+），可被巴弗洛霉素A1和肉毒毒素A抑制。ATP、轴突刺激和NP-EGTA的激光光解引起的嗅鞘细胞中的Ca 2+瞬变导致邻近血管的收缩。我们的研究结果表明，ATP和谷氨酸异位释放囊泡沿着轴突和介导神经血管耦合通过胶质细胞Ca 2+信号。
Neurotransmitter release generally is considered to occur at active zones of synapses, and ectopic release of neurotransmitters has been demonstrated in a few instances. However, the mechanism of ectopic neurotransmitter release is poorly understood. We took advantage of the intimate morphological and functional proximity of olfactory receptor axons and specialized glial cells, olfactory ensheathing cells (OECs), to study ectopic neurotransmitter release. Axonal stimulation evoked purinergic and glutamatergic Ca2+ responses in OECs, indicating ATP and glutamate release. In axons expressing synapto-pHluorin, stimulation evoked an increase in synapto-pHluorin fluorescence, indicative of vesicle fusion. Transmitter release was dependent on Ca2+ and could be inhibited by bafilomycin A1 and botulinum toxin A. Ca2+ transients in OECs evoked by ATP, axonal stimulation, and laser photolysis of NP-EGTA resulted in constriction of adjacent blood vessels. Our results indicate that ATP and glutamate are released ectopically by vesicles along axons and mediate neurovascular coupling via glial Ca2+ signaling.
影响因子：
3.6
作者：
Langer, David;Hammer, Klaus;Zimmermann, Herbert
通讯作者：
Zimmermann, Herbert
影响因子：
16.2
作者：
Stevens, B;Porta, S;Fields, RD
通讯作者：
Fields, RD