H2O2: a dynamic neuromodulator.
H2O2: a dynamic neuromodulator.
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H2O2：动态神经调节剂。
DOI：
10.1177/1073858411404531
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Rice ME
中科院分区：
文献类型：
--
作者：
Rice ME
越来越多的证据表明，过氧化氢(H2O2)是一种细胞内和细胞间的信号分子，可以影响从胚胎发育到细胞死亡的过程。大多数研究都集中在通过第二信使级联传递相对较慢的信号，大约在几分钟到几天的数量级。然而，H_2O_2也可以通过激活离子通道来介导亚秒信号。这一快速信号在黑质纹状体多巴胺(DA)通路中得到了最彻底的研究，该通路在促进由基底节介导的运动中起着关键作用。在黑质DA神经元中，内源性过氧化氢激活ATP敏感K+(KATP)通道，从而抑制DA神经元的放电。在纹状体，在中型棘神经元中，谷氨酸能AMPA受体激活下游产生的过氧化氢作为一种可扩散的信使，也通过KATP通道抑制轴突DA的释放。动态产生的过氧化氢的来源是线粒体的呼吸作用，因此，过氧化氢通过KATP通道在活性和代谢之间提供了一种新的联系。过氧化氢的其他靶标包括瞬时受体电位(Trp)通道。与H_2O_2通过KATP通道的抑制作用不同，Trp通道的激活是兴奋性的。这篇综述描述了过氧化氢在黑质纹状体通路和其他基底节神经元中作为信号媒介的新出现的作用。
Increasing evidence implicates hydrogen peroxide (H2O2) as an intra- and intercellular signaling molecule that can influence processes from embryonic development to cell death. Most research has focused on relatively slow signaling, on the order of minutes to days, via second messenger cascades. However, H2O2 can also mediate subsecond signaling via ion channel activation. This rapid signaling has been examined most thoroughly in the nigrostriatal dopamine (DA) pathway, which plays a key role in facilitating movement mediated by the basal ganglia. In DA neurons of the substantia nigra, endogenously generated H2O2 activates ATP-sensitive K+ (KATP) channels that inhibit DA neuron firing. In the striatum, H2O2 generated downstream from glutamatergic AMPA receptor activation in medium spiny neurons acts as a diffusible messenger that inhibits axonal DA release, also via KATP channels. The source of dynamically generated H2O2 is mitochondrial respiration; thus, H2O2 provides a novel link between activity and metabolism via KATP channels. Additional targets of H2O2 include transient receptor potential (TRP) channels. In contrast to the inhibitory effect of H2O2 acting via KATP channels, TRP channel activation is excitatory. This review describes emerging roles of H2O2 as a signaling agent in the nigrostriatal pathway and other basal ganglia neurons.