Endogenous PGE2 regulates membrane excitability and synaptic transmission in hippocampal CA1 pyramidal neurons
Endogenous PGE2 regulates membrane excitability and synaptic transmission in hippocampal CA1 pyramidal neurons
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DOI：
10.1152/jn.00696.2004
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发表时间：
2005-02-01
影响因子：
2.5
通讯作者：
Bazan, NG
中科院分区：
文献类型：
--
作者：
Chen, C;Bazan, NG
环氧合酶（COX）是将花生四烯酸（AA）转化为脑中的花生四烯酸（PGs）的限速酶，其意义尚不清楚，尽管它们与炎症反应和一些神经系统疾病如癫痫和阿尔茨海默病有关。最近的证据表明，考克斯-2，表达于突触后树突棘，在海马穿通通路-齿状颗粒细胞突触的活动依赖性长期突触可塑性中调节PGE（2）信号，提示考克斯-2产生的PGE（2）在突触信号中的重要作用。然而，很少有人知道内源性PGE（2）如何调节神经元信号。在这里，我们发现内源性PGE（2）选择性地调节海马的基本膜和突触特性。当用选择性考克斯-2抑制剂消除海马CA 1区锥体神经元内源性PGE（2）时，体细胞和树突细胞膜兴奋性显著降低。外源性PGE（2）可显著增加考克斯-2抑制剂处理的脑片的放电频率、兴奋性突触后电位（EPSP）振幅和时间总和。PGE（2）诱导的膜兴奋性增加似乎是由于其抑制钾电流，这反过来又增加了树突状细胞去极化电流注射过程中树突状细胞Ca ~（2+）内流。此外，PGE（2）诱导的EPSPs增强可通过消除PKA和PKC活性而被阻断。这些结果表明，内源性PGE（2）动态调节膜兴奋性，突触传递和可塑性，PGE（2）诱导的突触调制是通过cAMP PKA和PKC途径介导的大鼠海马CA 1区锥体神经元。
The significance of cyclooxygenases (COXs), the rate-limiting enzymes that convert arachidonic acid ( AA) to prostaglandins (PGs) in the brain, is unclear, although they have been implicated in inflammatory responses and in some neurological disorders such as epilepsy and Alzheimer's disease. Recent evidence that COX-2, which is expressed in postsynaptic dendritic spines, regulates PGE(2) signaling in activity-dependent long-term synaptic plasticity at hippocampal perforant path-dentate granule cell synapses, suggests an important role of the COX-2-generated PGE(2) in synaptic signaling. However, little is known of how endogenous PGE(2) regulates neuronal signaling. Here we showed that endogenous PGE(2) selectively regulates fundamental membrane and synaptic properties in the hippocampus. Somatic and dendritic membrane excitability was significantly reduced when endogenous PGE(2) was eliminated with a selective COX-2 inhibitor in hippocampal CA1 pyramidal neurons in slices. Exogenous application of PGE(2) produced significant increases in frequency of firing, excitatory postsynaptic potentials ( EPSP) amplitude, and temporal summation in slices treated with the COX-2 inhibitor. The PGE(2)-induced increase in membrane excitability seemed to result from its inhibition of the potassium currents, which in turn, boosted dendritic Ca2+ influx during dendritic-depolarizing current injections. In addition, the PGE(2)-induced enhancement of EPSPs was blocked by eliminating both PKA and PKC activities. These findings indicate that endogenous PGE(2) dynamically regulates membrane excitability, synaptic transmission, and plasticity and that the PGE(2)-induced synaptic modulation is mediated via cAMP-PKA and PKC pathways in rat hippocampal CA1 pyramidal neurons.