兴奋性氨基酸NMDA受体激动剂N-methyl-D-aspartate对大鼠海马CA_1区神经元膜电位影响  

The effects of N-methyl-D-aspartate on the membrane potential of neurons in CA_1 region in isolated hippocampal slices of rats

作　　者：张育才[1] 曾因明[2] 王钧[3] Ira Kass 

机构地区：[1]解放军第97医院麻醉科,江苏徐州221004 [2]徐州医学院江苏省麻醉医学研究所,江苏徐州221002 [3]美国纽约州立大学布鲁克林医学中心,美国纽约11203

出　　处：《中风与神经疾病杂志》2006年第1期49-51,共3页Journal of Apoplexy and Nervous Diseases

摘　　要：目的应用离体大鼠海马脑片,结合细胞内记录技术,研究兴奋性氨基酸NMDA受体激动剂N-methyl-D-aspartate对大鼠海马CA1区神经元膜电位的影响。方法海马脑片随机分为单纯缺氧组(Con组,n=10)、MK801组(n=10)和NMDA25μmol/L组(NMDA组,n=8)。Con组及MK801组的海马脑片分别给予10min缺氧或在缺氧期间应用含100μmol/L MK801的aCSF;NMDA组海马脑片在膜电位稳定15min后用含有25μmol/L NMDA的aCSF灌流10min。所有海马脑片均应用正常aCSF恢复60min。记录用药前或缺氧前膜电位、缓慢去极化的速率、快速去极化时间和快速去极化的幅度及恢复60min时神经元对细胞内注入电流及经Scheffer侧支刺激的反应。结果25μmol/L NMDA可以产生与缺氧相似的膜电位变化。但MK801组神经元的快速去极化时间显著高于NMDA组和Con组(P<0.05);NMDA组的快速去极化时间则显著短于Con组(P<0.05)。MK801组神经元的缓慢去极化速率为(0.08±0.03)mv/s,显著低于NMDA组的(0.44±0.12)mv/s及Con组的(0.22±0.05)mv/s(P<0.05)。在MK801组的10例神经元中,其中9例恢复对细胞内注入电流及经Schaffer刺激的反应,产生动作电位。结论兴奋性氨基酸NMDA受体的激活可能是神经元缺氧去极化的机制之一;而其受体拮抗剂MK801则可以显著抑制缺氧期间神经元膜电位的变化,促进复氧后神经元功能的恢复。Objective To investigate the effects of N methyl-D-aspartate and the blocker of NMDA receptor MK801 on the electrophysiological changes of neurons in the CA1 region of hippocampus in rats. Methods Hippocampus slices from adult male SDrats were divided into contral（Con） （n：10）,MK801 （n：10） and NMDA （n ：8） groups respectively. The slices in Con and MK801 groups were subjected to 10min of hypoxia,or given aCSF that had 100μmol/L MK801 during hypoxia,followed by 60min of re-oxygenation ;the slices in NMDA group were treated with aCSF which contained 25μmol/L NMDA for 10min,followed by normal aCSF for 60min. The rate of neuronal slow depolarization ,the time to rapid depolarization and the amplitude of rapid depolarization were recorded using intracellular recording technique. The neuronal response to the intracellular current injection and Schaffer collateral pathway stimuli was observed at the end of 60min period of recovery. Results The time to rapid depolarization in MK801 group was 537±139 seconds,which was significantly longer than 261±26 seconds in Con group and 162±8 seconds in NMDA group. Meanwhile,MK801 could inhibit the amplitude of neuronal rapid depolarization. There was no significant difference in the rate of slow depolarization of neurons in CAlregion during hy poxia in NMDA and Con group. But the rate of slow depolarization in MK801 group was significantly lower than thal in Con and NMDA groups. At the end of 60min of recovery with normal aCSF,9 out of 10 neurons in MK801 group had response to intracellular current injection and Schaffer collateral stimuli. But there was no recovery in NMDA and Con groups. Conclusion The activation of NMDA receptors of excitatory amino acid may be one of the mechanisms,which results in the depolarization of neurons in CA1 region of hippocampus during hypoxia,and the blocker of NMDA receptors can protect the neurons against hypoxic damage.

关 键 词：海马 人工脑脊液 缺氧 去极化 

分 类 号：R338.1[医药卫生—人体生理学]