【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。更多还原

【Abstract】 Objective The current study was designed to investigate the role of in the GluR1 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 Ser831 and Ser845 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. Results (1) The levels of phosphorylation of AMPA receptors GluR1 subunits in the spinal dorsal horn at Ser831 and Ser845 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 Ser831 and Ser845. Conclusion These results reveal that the phosphorylation of GluR1 at Ser831 and Ser845 is triggered by tetanus and regulated by CaMKⅡ.更多还原