Mechanisms underlying excitatory effects of group I metabotropic glutamate receptors via inhibition of 2P domain K+ channels
Mechanisms underlying excitatory effects of group I metabotropic glutamate receptors via inhibition of 2P domain K+ channels
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DOI：
10.1093/emboj/cdg528
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发表时间：
2003-10-15
期刊：
影响因子：
11.4
通讯作者：
Lazdunski, M
中科院分区：
文献类型：
--
作者：
Chemin, J;Girard, C;Lazdunski, M
I组代谢性谷氨酸受体（mGluRs）与学习、记忆、癫痫、疼痛和神经元死亡等多种过程有关。通过抑制背景K+通道，I组mglur介导缓慢而持久的兴奋。K+通道家族（K- 2p或KCNK）的主要神经元代表是TASK和TREK。在这里，我们发现在小脑颗粒细胞和异源表达系统中，I组mGluRs的激活抑制TASK和TREK通道。d-肌醇-1,4,5-三磷酸和磷脂酰-4,5-肌醇-二磷酸耗竭参与TASK通道抑制，而二酰基甘油和磷脂酸直接抑制TREK通道。这里描述的I组mGluRs的机制也可能代表许多其他激素和神经递质的受体。
Group I metabotropic glutamate receptors (mGluRs) are implicated in diverse processes such as learning, memory, epilepsy, pain and neuronal death. By inhibiting background K+ channels, group I mGluRs mediate slow and long-lasting excitation. The main neuronal representatives of this K+ channel family (K-2P or KCNK) are TASK and TREK. Here, we show that in cerebellar granule cells and in heterologous expression systems, activation of group I mGluRs inhibits TASK and TREK channels. d-myo-inositol-1,4,5-triphosphate and phosphatidyl-4,5-inositol-biphosphate depletion are involved in TASK channel inhibition, whereas diacylglycerols and phosphatidic acids directly inhibit TREK channels. Mechanisms described here with group I mGluRs will also probably stand for many other receptors of hormones and neurotransmitters.