Synaptic activation of transient receptor potential channels by metabotropic glutamate receptors in the lateral amygdala
Synaptic activation of transient receptor potential channels by metabotropic glutamate receptors in the lateral amygdala
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DOI：
10.1016/j.neuroscience.2005.09.027
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Sah, P
中科院分区：
文献类型：
--
作者：
Faber, ESL;Sedlak, P;Sah, P
经典的哺乳动物瞬时受体电位通道形成非选择性阳离子通道，该通道响应于磷脂酶C偶联的代谢性受体的激活而开放，被认为在非兴奋性细胞的钙稳态中起关键作用。在神经系统内，瞬时受体电位通道广泛分布，但其生理作用尚不清楚。在这里，我们表明，在大鼠杏仁核外侧，瞬时受体电位通道介导对谷氨酸的兴奋性突触反应。用外源性谷氨酸或突触释放的谷氨酸激活L组杏仁外侧锥体神经元上的内向谷氨酸受体，均可引起负电位下的内向电流，电流电压关系呈现负斜率和陡峭的外向整流区。这一电流可被GTP-β-S抑制G蛋白功能、抑制磷脂酶C或向杏仁核外侧锥体神经元注入瞬时受体潜在抗体所阻断。利用RT-PCR和Western blotting，我们发现杏仁外侧核存在瞬时受体电位1、瞬时受体电位4和瞬时受体电位5。单细胞聚合酶链式反应证实了锥体神经元中存在瞬时受体电位1和瞬时受体电位5，我们用免疫共沉淀法证明了瞬时受体电位1和瞬时受体电位5在杏仁核中作为异源多聚体共同组装。这些结果表明，在杏仁核外侧锥体神经元中，突触释放的谷氨酸激活了瞬时受体电位通道，我们认为这些通道很可能是包含瞬时受体电位1和瞬时受体电位5/瞬时受体电位4的异构体通道。(C)2005年由Elsevier Ltd代表IBRO发表。
Classical mammalian transient receptor potential channels form non-selective cation channels that open in response to activation of phospholipase C-coupled metabotropic receptors, and are thought to play a key role in calcium homeostasis in non-excitable cells. Within the nervous system transient receptor potential channels are widely distributed but their physiological roles are not well understood. Here we show that in the rat lateral amygdala transient receptor potential channels mediate an excitatory synaptic response to glutamate. Activation of group l etabotropic glutamate receptors on pyramidal neurons in the lateral amygdala with either exogenous or synaptically released glutamate evokes an inward current at negative potentials with a current voltage relationship showing a region of negative slope and steep outward rectification. This current is blocked by inhibiting G protein function with GTP-beta-S, by inhibiting phospholipase C or by infusing transient receptor potential antibodies into lateral amygdala pyramidal neurons. Using RT-PCR and Western blotting we show that transient receptor potential 1, transient receptor potential 4 and transient receptor potential 5 are present in the lateral amygdala. Single cell PCR confirms the presence of transient receptor potential 1 and transient receptor potential 5 in pyramidal neurons and we show by co-immunoprecipitation that transient receptor potential 1 and transient receptor potential 5 co-assemble as a heteromultimers in the amygdala. These results show that in lateral amygdala pyramidal neurons synaptically released glutamate activates transient receptor potential channels, which we propose are likely to be heteromultimeric channels containing transient receptor potential 1 and transient receptor potential 5/transient receptor potential 4. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.