Activation of ATP P2X receptors elicits glutamate release from sensory neuron synapses
Activation of ATP P2X receptors elicits glutamate release from sensory neuron synapses
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DOI：
10.1038/39639
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发表时间：
1997-10-16
期刊：
影响因子：
64.8
通讯作者：
MacDermott, AB
中科院分区：
文献类型：
--
作者：
Gu, JGG;MacDermott, AB
对皮肤的疼痛刺激在背根神经节（DRG）神经元的外周末梢中引发动作电位。这些动作电位传播到脊髓背角的DRG中央末梢，引起兴奋性递质如谷氨酸释放到突触后背角神经元上。P2 X受体是由内源性配体ATP激活的配体门控离子通道家族（1，2），由DRG神经元高度表达（3-5）。在与伤害性DRG中央终末相关的背角浅层中已发现对P2 X受体的免疫反应性（5），表明存在突触前P2 X受体。在这里，我们使用了背根神经节-背角共培养系统来表明P2 X受体定位于背根神经节神经元的突触前位点;这些受体的激活导致自发谷氨酸释放频率增加;并且在或附近激活P2 X受体突触前背根神经末梢会引发引起诱发谷氨酸释放的动作电位。因此，DRG中央终末的P2 X受体的激活可以改变感觉信号的通量，甚至可能在没有直接外周输入的情况下在中央突触处启动感觉信号。突触前P2 X受体可能参与痛觉的生理和病理过程，是疼痛治疗的一个重要靶点。
Painful stimuli to the skin initiate action potentials in the peripheral terminals of dorsal root ganglion (DRG) neurons. These action potentials propagate to DRG central terminals in the dorsal horn of the spinal cord, evoking release of excitatory transmitters such as glutamate onto postsynaptic dorsal horn neurons. P2X receptors, a family of ligand-gated ion channels(1,2) activated by the endogenous ligand ATP, are highly expressed by DRG neurons(3-5). Immunoreactivity to P2X receptors has been identified in the dorsal horn superficial laminae associated with nociceptive DRG central terminals(5), suggesting the presence of presynaptic P2X receptors. Here we have used a DRG-dorsal horn co-culture system to show that P2X receptors are localized at presynaptic sites on DRG neurons; that activation of these receptors results in increased frequency of spontaneous glutamate release; and that activation of P2X receptors at or near presynaptic DRG nerve terminals elicits action potentials that cause evoked glutamate release. Thus activation of P2X receptors at DRG central terminals can modify sensory signal throughput, and might even initiate sensory signals at central synapses without direct peripheral input. This putative central modulation and generation of sensory signals maybe associated with physiological and pathological pain sensation, making presynaptic P2X receptors a possible target for pain therapy.