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Facilitation of neurotransmittcr release through activation of presynaptic P_2X receptors by endogenous ATP

通过内源性 ATP 激活突触前 P_2X 受体促进神经递质释放

基本信息

批准号：
17300123
负责人：
KATO Fusao
金额：
$ 4.47万
依托单位：
Jikei University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17300123/
关键词：
P_2X receptors astrocvtes synaptic transmission transmitter release brain slice nucleus of the solitary tract glutamate gliotransmitter caged ATP laser photolysis

项目摘要

In aiming to clarify the interaction between astrocytes and neurons in native brain tissues through the intermediary of extracellular ATP-mediated signaling, I recorded postsynaptic currents of the neurons in the nucleus of the solitary tract (NTS) in transverse brainstem slices prepared from young Wistar rats and found the followings :1. Time- (100 ms) and space- (3 μm) delimited application of ATP using DMNPE-caged ATP and "flash-and-flush" application of laser beam onto dendrites of the neuron being recorded resulted in a marked increase in the frequency of spontaneous action potential-independent excitatory postsynaptic currents (EPSC). This glutamate release facilitation was almost completely abolished by PPADS (40 μM).2. The period of release facilitation was parallel to that of laser irradiation. The laser irradiation became ineffective after displacement of the beam by a few μm from the "hot.spot" on the dendrite. Under membrane potential recording without TTX but with Cd^<2+>, … More ATP uncaging resulted in an abrupt and short-lasting increase in the firing frequency of the recorded neuron.3. Fluoroacetate, a glia-specific toxin blocking TCA cycle, reduced the spontaneous EPSC frequency.4. A P_2Y_1 receptor agonist,2-methylthio-ADP, significantly increased EPSC frequency, an effect suppressed by a P_2X receptor blocker, trinitrophenyl ATP, and fluoroacetate.5. Trinitrophenyl ATP and A-317491, a P_2X_3-selective blocker, but not fluoroacetate and deletion of P_2X_4 protein abolished the release facilitation by a,β-methylene ATP.Altogether, these novel findings suggest that activation of astrocyte network in the NTS facilitates glutamate release though ATP release from astrocytes and subsequent activation of presynaptic P_2X_2/(3) receptors on the central terminals of the primary afferent fibers. This mechanism points to a possible ATP-mediated astrocyte-to-neuron signaling enabling astrocytes to promote excitatory transmission from the primary afferents to the second-order NTS neurons. Less

为了通过细胞外 ATP 介导的信号传导来阐明星形胶质细胞与天然脑组织中的神经元之间的相互作用，我在年轻 Wistar 大鼠制备的横向脑干切片中记录了孤束核 (NTS) 神经元的突触后电流，并发现了以下内容：1。使用 DMNPE 笼式 ATP 进行时间（100 ms）和空间（3 μm）限定的 ATP 应用，并将激光束“闪光和冲洗”应用到被记录的神经元树突上，导致自发动作电位独立的兴奋性突触后电流 (EPSC) 的频率显着增加。 PPADS (40 μM) 几乎完全消除了这种谷氨酸释放促进作用。2。释放促进期与激光照射期平行。光束从枝晶上的“热点”移动几微米后，激光照射变得无效。在没有 TTX 但使用 Cd^<2+> 的膜电位记录下，… 更多 ATP 解笼导致记录的神经元放电频率突然且短暂的增加。3。氟乙酸是一种神经胶质细胞特异性毒素，阻断TCA循环，降低自发EPSC频率。4． P_2Y_1 受体激动剂 2-甲硫基-ADP 显着增加 EPSC 频率，而 P_2X 受体阻滞剂、三硝基苯基 ATP 和氟乙酸酯可抑制这一作用。5．三硝基苯基 ATP 和 A-317491（一种 P_2X_3 选择性阻断剂），但不是氟乙酸盐，并且 P_2X_4 蛋白的删除消除了 a,β-亚甲基 ATP 的释放促进作用。总而言之，这些新发现表明，NTS 中星形胶质细胞网络的激活通过星形胶质细胞和星形胶质细胞释放 ATP 促进谷氨酸释放随后激活初级传入纤维中央末端的突触前 P_2X_2/(3) 受体。该机制表明可能存在 ATP 介导的星形胶质细胞至神经元信号传导，使星形胶质细胞能够促进从初级传入神经元到二级 NTS 神经元的兴奋性传递。较少的