Alteration of NMDA Response by Neuronal Injury

N-甲基-D-天冬氨酸（NMDA）受体在神经发育、神经元变性、神经元再生和突触可塑性中起重要作用。NMDA受体反应的最重要特征之一是细胞外Mg^<2+>及其高Ca^<2+>渗透性对该通道的电压依赖性阻断。在制备前1h至10天，在从接受颈部迷走神经挤压的大鼠体内新鲜分离的迷走神经背核（DMV）神经元上研究了电压依赖性Mg^<2+>阻断NMDA诱导反应的创伤后变化。电压依赖性Mg^<2+>对NMDA反应的阻断作用在损伤后至少12小时开始明显减弱，并持续到第5天，10天内恢复。在迷走神经轴突上局部应用秋水仙碱对Mg^<2+>的阻断没有影响，这表明神经元损伤如轴突挤压，而不是轴突流动的阻断，是导致NMDA对细胞外Mg^<2+>反应敏感性改变的原因。此外，在应用PKC调节剂如星形孢菌素、白屈菜红碱和钙磷素C时，神经损伤引起的Mg^<2 +>阻滞的减少持续存在，这表明轴突损伤后PKC活性的增加与这种变化无关。从这个意义上说，受损的DMV神经元重新获得了对细胞外Mg^2+敏感的不成熟特征。

N-methyl-D-aspartate (NMDA) receptors play important roles in neural development, neuronal degeneration, neuronal regeneration and synaptic plasticity. One of most important characteristics of NMDA receptor-response is voltage dependent block of this channel by extracellular Mg^<2+> as well as its high Ca^<2+> permeability. Post traumatic change of the voltage-dependent Mg^<2+> block of NMDA-induced response was investigated on the dorsal motor nucleus of vagus (DMV) neurons freshly dissociated from the rats receiving the vagaI nerve crush at the neck in vivo at hours to 10 days before making preparations. The reduction of voltage dependent Mg^<2+> block of NMDA response became evident at at least 12 hours after the injury, sustained until 5 days and recovered within 10 days. The Mg^<2+> block was not affected by the local application of colchicine onto the vagal axon, suggesting that the neuronal trauma such as axonal crush, not the blockade of the axonal flow, is responsible for the change of the sensitivity of NMDA response to extracellular Mg^<2+>. In addition, reduction of Mg^<2+> block by the nerve injury persisted in the applications of PKC modulators, such as staurosporine, chelerythrine and calphostin C, suggesting that increase of PKC activity after axonaI injury is not involved in this change.The NMDA receptor response was also less sensitive to Mg^<2+> in immature animals. in this sense, injured DMV neurons re-acquired immature characteristics regarding the sensitivity to extracellular Mg^<2+>.