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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

为了阐明星形胶质细胞和神经元之间通过细胞外ATP介导的信号传导的相互作用，我记录了年轻Wistar大鼠脑干横片孤束核（NTS）神经元的突触后电流，发现：1.用DMNPE-笼状ATP在时间（100 ms）和空间（3 μm）限定的条件下施加ATP和在被记录神经元树突上“一闪一闪”施加激光束导致自发动作电位非依赖性兴奋性突触后电流（EPSC）频率显著增加。PPADS（40 μM）几乎完全消除了这种谷氨酸释放促进作用.释放促进期与激光照射时间相平行。在枝晶上将光束从“hot.spot“位移几μm后，激光照射变得无效。在不加TTX而加Cd^<2+>的膜电位记录下， ...更多信息 ATP去包裹导致记录的神经元放电频率的突然和短暂的增加。氟乙酸是一种胶质细胞特异性毒素，阻断TCA循环，降低自发EPSC频率. P_2Y_1受体激动剂2-methylthio-ADP能显著增加EPSC频率，而P_2X受体阻断剂三硝基苯基ATP和氟乙酸则能抑制这种作用.三硝基苯基ATP和P_2X_3选择性阻断剂A-317491（但氟乙酸和P_2X_4蛋白的缺失不能阻断α，β-亚甲基ATP的促释作用）均能阻断α，β-亚甲基ATP的促释作用。这些新的发现表明，NTS中星形胶质细胞网络的激活通过星形胶质细胞释放ATP促进谷氨酸的释放，并随后激活突触前P_2X_2/（3）。初级传入纤维的中央末梢上的受体。这一机制表明，可能是ATP介导的星形胶质细胞-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。少