The chemokine interleukin-8 acutely reduces Ca2+ currents in identified cholinergic septal neurons expressing CXCR1 and CXCR2 receptor mRNAs
The chemokine interleukin-8 acutely reduces Ca2+ currents in identified cholinergic septal neurons expressing CXCR1 and CXCR2 receptor mRNAs
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DOI：
10.1046/j.1471-4159.2001.00469.x
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发表时间：
2001-09-01
影响因子：
4.7
通讯作者：
Williams, S
中科院分区：
文献类型：
--
作者：
Puma, C;Danik, M;Williams, S
已知趋化因子IL-8由脑中的神经胶质细胞合成。传统上它已被证明在神经炎症中具有重要作用，但最近的证据表明它也可能参与神经元中的快速信号传导。我们研究了如何IL-8参与快速神经元信号通过使用分离的大鼠隔神经元的全细胞记录和单细胞RT-PCR相结合。我们发现IL-8可以急性降低隔神经元的Ca 2+电流，这种作用是浓度依赖性的，涉及L型和N型Ca 2+通道的关闭，以及G蛋白G（i α 1）和/或G（i α 2）亚型的激活。对记录的神经元的mRNA的分析表明，后者本质上都是胆碱能的。此外，我们发现所有对IL-8有反应的胆碱能神经元表达IL-8受体CXCR 1和CXCR 2中的一种或两种的mRNA。这是第一次报道通过G蛋白调节神经元离子通道的趋化因子，也是第一次证明CXCR 1的mRNA在大脑中表达。我们的研究结果表明，IL-8释放的胶质细胞在体内可能激活CXCR 1和CXCR 2受体胆碱能隔神经元和急性调节其兴奋性通过关闭钙通道。
The chemokine IL-8 is known to be synthesized by glial cells in the brain. It has traditionally been shown to have an important role in neuroinflammation but recent evidence indicates that it may also be involved in rapid signaling in neurons. We investigated how IL-8 participates in rapid neuronal signaling by using a combination of whole-cell recording and single-cell RT-PCR on dissociated rat septal neurons. We show that IL-8 can acutely reduce Ca2+ currents in septal neurons, an effect that was concentration-dependent, involved the closure of L- and N-type Ca2+ channels, and the activation of G(i alpha1) and/or G(i alpha2) subtype(s) of G-proteins. Analysis of the mRNAs from the recorded neurons revealed that the latter were all cholinergic in nature. Moreover, we found that all cholinergic neurons that responded to IL-8, expressed mRNAs for either one or both IL-8 receptors CXCR1 and CXCR2. This is the first report of a chemokine that modulates ion channels in neurons via G-proteins, and the first demonstration that mRNAs for CXCR1 are expressed in the brain. Our results suggest that IL-8 release by glial cells in vivo may activate CXCR1 and CXCR2 receptors on cholinergic septal neurons and acutely modulate their excitability by closing calcium channels.