Zhang X, Chen Y, Wang C, Huang L-Y M
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-1069, USA.
Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9864-9. doi: 10.1073/pnas.0611048104. Epub 2007 May 24.
It has been generally assumed that the cell body (soma) of a neuron, which contains the nucleus, is mainly responsible for synthesis of macromolecules and has a limited role in cell-to-cell communication. Using sniffer patch recordings, we show here that electrical stimulation of dorsal root ganglion (DRG) neurons elicits robust vesicular ATP release from their somata. The rate of release events increases with the frequency of nerve stimulation; external Ca(2+) entry is required for the release. FM1-43 photoconversion analysis further reveals that small clear vesicles participate in exocytosis. In addition, the released ATP activates P2X7 receptors in satellite cells that enwrap each DRG neuron and triggers the communication between neuronal somata and glial cells. Blocking L-type Ca(2+) channels completely eliminates the neuron-glia communication. We further show that activation of P2X7 receptors can lead to the release of tumor necrosis factor-alpha (TNFalpha) from satellite cells. TNFalpha in turn potentiates the P2X3 receptor-mediated responses and increases the excitability of DRG neurons. This study provides strong evidence that somata of DRG neurons actively release transmitters and play a crucial role in bidirectional communication between neurons and surrounding satellite glial cells. These results also suggest that, contrary to the conventional view, neuronal somata have a significant role in cell-cell signaling.
人们普遍认为,含有细胞核的神经元细胞体(胞体)主要负责大分子的合成,在细胞间通讯中作用有限。通过嗅探膜片钳记录,我们在此表明,对背根神经节(DRG)神经元进行电刺激会引发其胞体大量释放囊泡ATP。释放事件的速率随神经刺激频率增加而增加;释放需要细胞外Ca(2+)内流。FM1-43光转化分析进一步揭示,小而清亮的囊泡参与胞吐作用。此外,释放的ATP激活包裹每个DRG神经元的卫星细胞中的P2X7受体,并触发神经元胞体与神经胶质细胞之间的通讯。阻断L型Ca(2+)通道可完全消除神经元-神经胶质细胞通讯。我们进一步表明,P2X7受体的激活可导致卫星细胞释放肿瘤坏死因子-α(TNFα)。TNFα反过来增强P2X3受体介导的反应并增加DRG神经元的兴奋性。本研究提供了强有力的证据,表明DRG神经元的胞体积极释放递质,并在神经元与周围卫星神经胶质细胞之间的双向通讯中起关键作用。这些结果还表明,与传统观点相反,神经元胞体在细胞间信号传导中具有重要作用。