Modulation of transient receptor potential Vanilloid 4-mediated membrane currents and synaptic transmission by protein kinase C.
Modulation of transient receptor potential Vanilloid 4-mediated membrane currents and synaptic transmission by protein kinase C.
复制标题
DOI：
10.1186/1744-8069-5-5
复制
发表时间：
2009-02-10
期刊：
影响因子：
3.3
通讯作者：
Premkumar LS
中科院分区：
文献类型：
--
作者：
Cao DS;Yu SQ;Premkumar LS
瞬时受体电位香草酸（TRPV）受体参与伤害感受并且主要在感觉神经元中表达。TRPV 1是一种非选择性阳离子通道，已被广泛研究，并负责炎性热超敏反应。在这项研究中，TRPV 4的表达和功能的特点，并与TRPV 1。免疫组化结果显示，TRPV 1和TRPV 4在背根神经节（DRG）神经元胞体和脊髓背角（DH）I、II层的中央终末共表达。在Ca 2+荧光成像和全细胞膜片钳实验中，在相同DRG神经元的群体中观察到TRPV 1和TRPV 4介导的反应。TRPV 1的致敏作用已被证明与炎症性疼痛有关。与PKC激活剂佛波醇12，13-二丁酸酯（PDBu）孵育，导致DRG神经元TRPV 4电流显著增强。在表达TRPV 4的HEK 293 T细胞中，PDBu增加了4α-佛波醇12，13-二癸酸酯（4α-PDD）诱导的细胞贴附贴片中的单通道活性，这被双吲哚马来酰亚胺（BIM）（一种选择性PKC抑制剂）废除。TRPV 4也在感觉神经元的中枢末梢表达。4α-PDD激活TRPV 4可增加DRG-DH神经元共培养物中的微小兴奋性突触后电流（mEPSC）频率。PDBu进一步增强了4α-PDD诱导的mEPSC频率增加。TRP通道的表达已在CNS的其他区域显示; 4α-PDD的应用显著增加了培养的海马神经元中的mEPSC频率，PDBu进一步增强了该频率，而TRPV 1激动剂辣椒素不调节突触传递。这些结果表明，TRPV 4和TRPV 1在某些DRG神经元中共表达，并且TRPV 4不仅在DRG神经元胞体中，而且在中枢感觉和非感觉神经末梢中被PKC敏化。TRPV 1和TRPV 4离子通道的共表达、它们对突触传递的调节以及它们通过PKC的增敏作用可能在伤害性感受中协同发挥作用。
Transient receptor potential Vanilloid (TRPV) receptors are involved in nociception and are expressed predominantly in sensory neurons. TRPV1, a non-selective cation channel has been extensively studied and is responsible for inflammatory thermal hypersensitivity. In this study, the expression and function of TRPV4 have been characterized and compared with those of TRPV1. Immunohistochemical studies revealed that both TRPV1 and TRPV4 were co-expressed in dorsal root ganglion (DRG) neuronal cell bodies and in the central terminals of laminae I and II of the spinal dorsal horn (DH). In Ca2+ fluorescence imaging and whole-cell patch-clamp experiments, TRPV1- and TRPV4-mediated responses were observed in a population of the same DRG neurons. Sensitization of TRPV1 has been shown to be involved in inflammatory pain conditions. Incubation with phorbol 12, 13-dibutyrate (PDBu), a PKC activator, resulted in a significant potentiation of TRPV4 currents in DRG neurons. In TRPV4 expressing HEK 293T cells, PDBu increased 4α-phorbol 12, 13-didecanoate (4α-PDD)-induced single-channel activity in cell-attached patches, which was abrogated by bisindolylmaleimide (BIM), a selective PKC inhibitor. TRPV4 is also expressed at the central terminals of sensory neurons. Activation of TRPV4 by 4α-PDD increased the frequency of miniature excitatory post synaptic currents (mEPSCs) in DRG-DH neuronal co-cultures. 4α-PDD-induced increase in the frequency of mEPSCs was further enhanced by PDBu. The expression of TRP channels has been shown in other areas of the CNS; application of 4α-PDD significantly increased the mEPSC frequency in cultured hippocampal neurons, which was further potentiated by PDBu, whereas, TRPV1 agonist capsaicin did not modulate synaptic transmission. These results indicate that TRPV4 and TRPV1 are co-expressed in certain DRG neurons and TRPV4 can be sensitized by PKC not only in DRG neuronal cell bodies, but also in the central sensory and non-sensory nerve terminals. Co-expression of TRPV1 and TRPV4 ion channels, their modulation of synaptic transmission and their sensitization by PKC may synergistically play a role in nociception.
登录
查看更多内容
DOI：
10.1073/pnas.1735416100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Liedtke, W;Friedman, JM
通讯作者：
Friedman, JM
影响因子：
5.3
作者：
Alessandri-Haber, N;Dina, OA;Levine, JD
通讯作者：
Levine, JD
影响因子：
3.3
作者：
Cristino, L.;De Petrocellis, L.;Di Marzo, V.
通讯作者：
Di Marzo, V.
影响因子：
4.8
作者：
Chung, MK;Lee, H;Caterina, MJ
通讯作者：
Caterina, MJ
影响因子：
5.5
作者：
Baccei, ML;Bardoni, R;Fitzgerald, M
通讯作者：
Fitzgerald, M