Substance P Activates Ca2+-Permeable Nonselective Cation Channels through a Phosphatidylcholine-Specific Phospholipase C Signaling Pathway in nNOS-Expressing GABAergic Neurons in Visual Cortex
Substance P Activates Ca2+-Permeable Nonselective Cation Channels through a Phosphatidylcholine-Specific Phospholipase C Signaling Pathway in nNOS-Expressing GABAergic Neurons in Visual Cortex
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DOI：
10.1093/cercor/bhu233
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发表时间：
2016-02-01
期刊：
影响因子：
3.7
通讯作者：
Komatsu, Yukio
中科院分区：
文献类型：
--
作者：
Endo, Toshiaki;Yanagawa, Yuchio;Komatsu, Yukio
为了理解新皮层的功能，必须描述构成皮层回路的神经元的特性。在这里，我们专注于一个独特的GABA能神经元，这是由神经元型一氧化氮合酶（nNOS）和P物质（SP）受体[神经激肽1（NK 1）受体]的强烈标记的特定共定位定义的。我们研究了SP对谷氨酸脱羧酶67-绿色荧光蛋白基因敲入小鼠视皮层脑片中这些神经元的作用机制。浴应用SP诱导的非选择性阳离子电流导致去极化，抑制nNOS免疫阳性神经元中的NK 1拮抗剂。瞬时受体电位（TRP）通道阻断剂钌红和镧离子抑制SP诱导的电流。SP诱导的电流由G蛋白介导，并被磷脂酰胆碱特异性磷脂酶C（PC-PLC）抑制剂D 609抑制，但不被磷脂酰肌醇特异性PLC、腺苷酸环化酶或Src酪氨酸激酶抑制剂抑制。电压钳下的Ca ~（2+）成像实验表明，SP诱导的细胞内Ca ~（2+）升高可被细胞外Ca ~（2+）的清除所消除，但不被细胞内Ca ~（2+）库的耗尽所消除。这些结果表明，SP调节nNOS神经元激活TRP样钙渗透性非选择性阳离子通道通过PC PLC依赖的信号通路。
To understand the functions of the neocortex, it is essential to characterize the properties of neurons constituting cortical circuits. Here, we focused on a distinct group of GABAergic neurons that are defined by a specific colocalization of intense labeling for both neuronal nitric oxide synthase (nNOS) and substance P (SP) receptor [neurokinin 1 (NK1) receptors]. We investigated the mechanisms of the SP actions on these neurons in visual cortical slices obtained from young glutamate decarboxylase 67-green fluorescent protein knock-in mice. Bath application of SP induced a nonselective cation current leading to depolarization that was inhibited by the NK1 antagonists in nNOS-immunopositive neurons. Ruthenium red and La3+, transient receptor potential (TRP) channel blockers, suppressed the SP-induced current. The SP-induced current was mediated by G proteins and suppressed by D609, an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), but not by inhibitors of phosphatidylinositol-specific PLC, adenylate cyclase or Src tyrosine kinases. Ca2+ imaging experiments under voltage clamp showed that SP induced a rise in intracellular Ca2+ that was abolished by removal of extracellular Ca2+ but not by depletion of intracellular Ca2+ stores. These results suggest that SP regulates nNOS neurons by activating TRP-like Ca2+-permeable nonselective cation channels through a PC-PLC-dependent signaling pathway.