PROTEIN-KINASE-C REDUCES MG2+ BLOCK OF NMDA-RECEPTOR CHANNELS AS A MECHANISM OF MODULATION
PROTEIN-KINASE-C REDUCES MG2+ BLOCK OF NMDA-RECEPTOR CHANNELS AS A MECHANISM OF MODULATION
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DOI：
10.1038/356521a0
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发表时间：
1992-04-09
期刊：
影响因子：
64.8
通讯作者：
HUANG, LYM
中科院分区：
文献类型：
--
作者：
CHEN, L;HUANG, LYM
THF 对 N-甲基-D-天冬氨酸 (NMDA) 受体和蛋白激酶 C (PKC) 的作用对于产生和维持各种持续的神经元反应至关重要。在伤害感受（疼痛感知）系统中，组织损伤或小直径传入纤维的重复刺激会引发脊髓神经元放电（缠绕）的急剧增加或延长的去极化。当 NMDA 受体通道被阻断时，这种中枢敏化既不能被诱导也不能维持 1,2。在三叉神经尾亚核（处理口面部区域伤害性信息的中心 3）中，mu-阿片受体激动剂通过激活细胞内 PKC 4 引起 NMDA 激活电流持续增加。还有证据表明 PKC 增强 NMDA 受体介导的谷氨酸反应 4-7 并调节突触传递的长期增强 8-14。尽管 NMDA 受体和 PKC 很重要，但 PKC 改变 NMDA 反应的机制仍不清楚。在这里，我们研究了细胞内应用的 PKC 对分离的三叉神经元中 NMDA 激活电流的作用。我们发现 PKC 通过增加通道开放的概率和减少 NMDA 受体通道的电压依赖性 Mg2+ 阻断来增强 NMDA 响应。
THF roles of N-methyl-D-aspartate (NMDA) receptors and protein kinase C (PKC) are critical in generating and maintaining a variety of sustained neuronal responses. In the nociceptive (pain-sensing) system, tissue injury or repetitive stimulation of small-diameter afferent fibres triggers a dramatic increase in discharge (wind-up) or prolonged depolarization of spinal cord neurons. This central sensitization can neither be induced nor maintained when NMDA receptor channels are blocked 1,2. In the trigeminal subnucleus caudalis (a centre for processing nociceptive information from the orofacial areas 3), a mu-opioid receptor agonist causes a sustained increase in NMDA-activated currents by activating intracellular PKC 4. There is also evidence that PKC enhances NMDA-receptor-mediated glutamate responses 4-7 and regulates long-term potentiation of synaptic transmission 8-14. Despite the importance of NMDA-receptors and PKC, the mechanism by which PKC alters the NMDA response has remained unclear. Here we examine the actions of intracellularly applied PKC on NMDA-activated currents in isolated trigeminal neurons. We find that PKC potentiates the NMDA response by increasing the probability of channel openings and by reducing the voltage-dependent Mg2+ block of NMDA-receptor channels.