CaMK Ⅱ在脊髓背角LTP中调节AMPA受体GluR1亚单位的磷酸化  

CaMK Ⅱ Regulates Phosphorylation of GluR1 Subunit of AMPA Receptors in Long-Term Potentiation of C-Fiber Evoked Field Potentials in Rat Spinal Dorsal Horn

作　　者：信文君[1] 许继田[2] 宫庆娟[1] 魏绪红[1] 张彤[1] 李永勇[1] 刘先国[1] 

机构地区：[1]中山大学中山医学院生理教研室,广东广州510089 [2]郑州大学医学院生理教研室,河南郑州450000

出　　处：《中山大学学报（医学科学版）》2007年第3期241-245,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(30200076;30370474;30570599);广东省自然科学基金(5300603);广东省医学科研基金(A2006174)

摘　　要：【目的】研究钙/钙调素调依赖性蛋白激酶Ⅱ(CaMKⅡ)在大鼠脊髓背角C纤维诱发电位长时程增强(LTP)中对α-氨基羟甲基异噁唑丙酸(AMPA)受体GluR1亚单位磷酸化的影响,探讨长时程增强的分子机制。【方法】利用电生理和Western blot方法,检测脊髓背角LTP后30min和3hAMPA受体GluR1亚单位Ser831和Ser845位点磷酸化水平,同时在强直刺激前,脊髓局部给予CaMKⅡ特异性抑制剂KN-93,检测GluR1亚单位Ser831和Ser845磷酸化水平变化。【结果】强直刺激后30min、3h,脊髓背角AMPA受体GluR1亚单位Ser831和Ser845磷酸化水平明显增加。脊髓背角局部给予KN-93,阻断了LTP的诱导并且也阻止了GluR1亚单位Ser831和Ser845磷酸化水平的增加。【结论】强直刺激可导致GluR1亚单位Ser831和Ser845激活且它的激活可能是通过CaMKⅡ来实现的。[Objective] The current study was designed to investigate the role of in the GluRI subuint of α- amino-3-hydroxy-5-methyl-4-isoxazole propionate （AMPA） receptors in the long-term potentiation （LTP） of C- fiber evoked field potentials in rat spinal dorsal horn, and elucidate the mechanism of the spinal LTP. [Methods] The phosphorylation of GluR1 subunits at Ser^831 and Ser^845 were examined in the lumbar segments of the rat spinal dorsal horn at 30 min and 3 h by tetanic electrical stimulation of the sciatic nerve by using Western blot and eletrophysiological techniques. [Resuhs] （1） The levels of phosphorylation of AMPA receptors GluR1 subunits in the spinal dorsal horn at Ser^831 and Ser^845 were significantly increased at 30 min and 3 h after tetanic stimulation. （2） Spinal application of KN-93, a CaMKⅡ inhibitor, blocked the spinal LTP and prevented the phosphorylation of GluR1 subunits at Ser^831 and Ser^845. [Conclusion] These results reveal that the phosphorylation of GluR1 at Ser^831 and Ser^845 is triggered by tetanus and regulated by CaMKⅡ.

关 键 词：钙调依赖性蛋白激酶Ⅱ 长时程增强 GLUR1 KN-93 磷酸化作用 脊髓背角 

分 类 号：R338.2[医药卫生—人体生理学]