Chemin Jean, Girard Christophe, Duprat Fabrice, Lesage Florian, Romey Georges, Lazdunski Michel
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS - UMR 6097, Institut Paul Hamel, 660, Route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
EMBO J. 2003 Oct 15;22(20):5403-11. doi: 10.1093/emboj/cdg528.
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.
I 型代谢型谷氨酸受体（mGluRs）参与多种生理过程，如学习、记忆、癫痫、疼痛和神经元死亡。通过抑制背景钾离子通道，I 型 mGluRs介导缓慢且持久的兴奋。该钾离子通道家族（K(2P) 或 KCNK）的主要神经元代表是 TASK 和 TREK。在此，我们表明，在小脑颗粒细胞和异源表达系统中，I 型 mGluRs 的激活会抑制 TASK 和 TREK 通道。D-肌醇-1,4,5-三磷酸和磷脂酰-4,5-二磷酸的消耗参与 TASK 通道的抑制，而二酰基甘油和磷脂酸直接抑制 TREK 通道。这里描述的 I 型 mGluRs 的机制可能也适用于许多其他激素和神经递质受体。
