Abteilung für Allgemeine Zoologie, Technische Universität Kaiserslautern, 67653 Kaiserslautern, Germany.
Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15258-63. doi: 10.1073/pnas.1003501107. Epub 2010 Aug 9.
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 Ca(2+) 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 Ca(2+) and could be inhibited by bafilomycin A1 and botulinum toxin A. Ca(2+) 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 Ca(2+) signaling.
神经递质释放通常被认为发生在突触的活动区，并且已经在少数情况下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还不清楚。我们利用嗅觉受体轴突和专门的神经胶质细胞，即嗅鞘细胞（OEC）之间的紧密形态和功能接近性，来研究异位神经递质释放。轴突刺激在 OEC 中诱发嘌呤能和谷氨酸能 Ca(2+)反应，表明 ATP 和谷氨酸的释放。在表达突触 pHluorin 的轴突中，刺激引发突触 pHluorin 荧光的增加，表明囊泡融合。递质释放依赖于 Ca(2+)，可以被巴弗洛霉素 A1 和肉毒毒素 A 抑制。由 ATP、轴突刺激和 NP-EGTA 的激光光解在 OEC 中引起的 Ca(2+)瞬变导致相邻血管的收缩。我们的结果表明，ATP 和谷氨酸通过囊泡沿着轴突异位释放，并通过神经胶质细胞 Ca(2+)信号传导介导神经血管偶联。
