Inflammation alters cation chloride cotransporter expression in sensory neurons
Inflammation alters cation chloride cotransporter expression in sensory neurons
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DOI：
10.1016/j.nbd.2004.05.010
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发表时间：
2004-10-01
影响因子：
6.1
通讯作者：
Donaldson, LF
中科院分区：
文献类型：
--
作者：
Morales-Aza, BM;Chillingworth, NL;Donaldson, LF
阳离子氯化物协同转运蛋白被认为在调节神经元对 γ-氨基丁酸 (GABA) 的反应中发挥作用。在神经元损伤的情况下，神经元兴奋性增加，KCC2 转运蛋白的表达减少。这在神经性疼痛模型的脊髓中也可见到。我们研究了关节炎期间背根神经节 (DRG) 和脊髓感觉神经元中 Na-K-Cl 和 K-Cl 协同转运蛋白 NKCC1 和 KCC2 的表达，在关节炎中神经元兴奋性也会增加。 NKCC1 在对照 DRG 神经元中表达，并且其表达在关节炎中降低。 NKCC1 和 KCC2 均在脊髓的感觉神经元中表达。在急性关节炎中，NKCC1和KCC2 mRNA在浅表背角而非深层背角中增加，并且伴随着蛋白质表达的增加。在慢性关节炎中，NKCC1 表达仍然升高，但 KCC2 mRNA 和蛋白表达恢复到控制水平。关节炎中 KCC2 和 NKCC1 表达的改变可能有助于控制脊髓兴奋性，并可能代表治疗炎性疼痛的新治疗靶点。 (C) 2004 Elsevier Inc. 保留所有权利。
Cation chloride cotransporters have been proposed to play a role in the modulation of neuronal responses to gamma-aminobutyric acid (GABA). In conditions of neuronal damage, where neuronal excitability is increased, the expression of the KCC2 transporter is decreased. This is also seen in spinal cord in models of neuropathic pain. We have investigated the expression of the Na-K-Cl, and K-Cl cotransporters NKCC1 and KCC2, in dorsal root ganglion (DRG) and spinal sensory neurons during arthritis, a condition in which neuronal excitability is also increased. NKCC1 was expressed in control DRG neurons, and its expression was decreased in arthritis. Both NKCC1 and KCC2 were expressed in sensory neurons in the spinal cord. In acute arthritis, both NKCC1 and KCC2 mRNA increased in superficial but not deep dorsal horn, and this was accompanied by an increase in protein expression. In chronic arthritis, NKCC1 expression remained raised, but KCC2 mRNA and protein expression returned to control levels. Altered KCC2 and NKCC1 expression in arthritis may contribute to the control of spinal cord excitability and may represent novel therapeutic targets in the treatment of inflammatory pain. (C) 2004 Elsevier Inc. All rights reserved.