PKCα is required for inflammation-induced trafficking of extrasynaptic AMPA receptors in tonically firing lamina II dorsal horn neurons during the maintenance of persistent inflammatory pain.
PKCα is required for inflammation-induced trafficking of extrasynaptic AMPA receptors in tonically firing lamina II dorsal horn neurons during the maintenance of persistent inflammatory pain.
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DOI：
10.1016/j.jpain.2012.10.015
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发表时间：
2013-02
期刊：
影响因子：
4
通讯作者：
Voitenko, Nana
中科院分区：
文献类型：
--
作者：
Kopach, Olga;Viatchenko-Karpinski, Viacheslav;Atianjoh, Fidelis E.;Belan, Pavel;Tao, Yuan-Xiang;Voitenko, Nana
持续的炎症促进含有Ca2+不渗透的突触glur2的AMPA受体（AMPARs）的内化和含有glur1的Ca2+渗透性AMPARs在背角神经元的突触外位置的插入。先前我们已经表明，突触中含有glur2的AMPARs的内化需要脊髓蛋白激酶Cα (PKCα)的激活，但是突触外AMPARs转运改变的分子机制仍然不清楚。通过利用特异性敲除PKCα的反义寡脱氧核苷酸，我们发现背角PKCα表达的减少阻止了大鼠脊髓明胶质（SG）神经元中完全弗氏佐剂（CFA）诱导的突触外Ca2+通透性AMPARs功能表达的增加。这表现为ampa诱导的增强电流和相关的[Ca2+]i瞬态的消除，并且与cfa后1 d的电流整流相反。这些变化在具有内在紧张性放电特性的SG神经元中观察到，而在表现出强适应性的神经元中没有观察到。最后，背角PKCα敲低对炎症性疼痛维持期cfa诱导的热、机械超敏反应具有抗伤害性作用，提示PKCα在持续性炎症性疼痛维持中发挥作用。总之，我们的研究结果表明，炎症诱导的突触外Ca2+渗透性AMPARs在强直放电的SG神经元中的运输依赖于PKCα，并表明这种PKCα依赖性的运输可能有助于持续炎性疼痛的维持。
Persistent inflammation promotes internalization of synaptic GluR2-containing Ca2+-impermeable AMPA receptors (AMPARs) and insertion of GluR1-containing Ca2+-permeable AMPARs at extrasynaptic sites in dorsal horn neurons. Previously we have shown that internalization of synaptic GluR2-containing AMPARs requires an activation of spinal cord protein kinase C alpha (PKCα), but molecular mechanisms that underlie altered trafficking of extrasynaptic AMPARs are still unclear. By utilizing the antisence oligodeoxynucleotides that specifically knockdown PKCα, we have found that a decrease in dorsal horn PKCα expression prevents complete Freund’s adjuvant (CFA)-induced increase in a functional expression of extrasynaptic Ca2+-permeable AMPARs in substantia gelatinosa (SG) neurons of the rat spinal cord. This was manifested as an abolishment of augmented AMPA-induced currents and associated [Ca2+]i transients, and as a reverse of the current rectification 1 d post-CFA. These changes were observed specifically in SG neurons characterized by intrinsic tonic firing properties, but not in those exhibiting strong adaptation. Finally, dorsal horn PKCα knockdown produced anti-nociceptive effect on CFA-induced thermal and mechanical hypersensitivity during the maintenance period of inflammatory pain, indicating a role for PKCα in persistent inflammatory pain maintenance. Altogether, our results indicate that inflammation-induced trafficking of extrasynaptic Ca2+-permeable AMPARs in tonically firing SG neurons depends on PKCα, and suggest that this PKCα-dependent trafficking may contribute to the persistent inflammatory pain maintenance.
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脊髓α-Amino-3-羟基-5-甲基-4-异恶唑丙酸受体受体的作用在完整的弗朗德辅助引起的炎症性疼痛中。
影响因子：
3.3
作者：
Park JS;Yaster M;Guan X;Xu JT;Shih MH;Guan Y;Raja SN;Tao YX
通讯作者：
Tao YX
影响因子：
5.5
作者：
Santos, Sonia F. A.;Rebelo, Sandra;Safronov, Boris V.
通讯作者：
Safronov, Boris V.
影响因子：
5.3
作者：
Guire, Eric S.;Oh, Michael C.;Derkach, Victor A.
通讯作者：
Derkach, Victor A.
影响因子：
56.9
作者：
Heine, Martin;Groc, Laurent;Choquet, Daniel
通讯作者：
Choquet, Daniel
影响因子：
3.4
作者：
Katano, Tayo;Furue, Hidemasa;Ito, Seiji
通讯作者：
Ito, Seiji