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大鼠下丘培养神经元上NMDA与GABAA受体之间的交互作用

, PP. 361-368

Keywords: 下丘,N-甲基-D-门冬氨酸受体,&gamma,-氨基丁酸A型受体,全细胞膜片钳,交互作用

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Abstract:

在中枢神经系统中,不同类型的神经元的离子通道往往是通过相互作用而非独立地发挥其功能的,例如,激活一种通道能够抑制或增强另一种通道的功能.N-甲基-D-门冬氨酸受体(NMDA受体)和γ-氨基丁酸A型受体(GABAA受体)分别是中枢神经系统中重要的兴奋性和抑制性的受体.目前,在中枢神经系统中,尤其是在中枢听觉系统中,关于这两种受体的交互作用还没有被详尽地研究.下丘是中枢听觉系统中重要的神经核团.本实验中,在培养的下丘神经元细胞上,利用全细胞膜片钳技术研究了NMDA受体和GABAA受体之间的功能性交互作用.结果发现:(1)100μmol/L的GABA可抑制100μmol/LAsp在下丘神经元激活的全细胞电流(IAsp),表明GABAA受体的激活能够抑制NMDA受体的功能;(2)100μmol/L的Asp对高浓度(100μmol/L)GABA在下丘神经元激活的全细胞电流(IGABA)没有影响,但对低浓度(3μmol/L)GABA激活的IGABA有抑制作用,表明NMDA受体的激活对GABAA受体的抑制作用是浓度依赖性的;(3)细胞外液中加入电压依赖的钙通道(VDCCs)的阻断剂CdCl2不影响Asp对IGABA的抑制作用,但当外液中无钙或在电极内液中加入钙的螯合剂BAPTA时,Asp对IGABA的抑制作用消失,说明这种抑制作用是由钙离子介导的,并且是钙离子通过NMDA受体通道内流而非经由VDCCs内流而发挥作用的;(4)Asp对IGABA的抑制作用可被钙-钙调素依赖性的蛋白激酶Ⅱ(CaMKⅡ)的抑制剂KN-62所阻断,说明在NMDA受体和GABAA受体的功能交互作用中,CaMKⅡ起到了重要的作用.本研究表明,在培养的大鼠下丘神经元上的NMDA受体和GABAA受体之间存在着功能性的交互作用,这两种受体通道之间的交互作用暗示了中枢听觉系统中对于信息加工这一过程可能有着更为复杂的机制.

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