Robert A, Black J A, Waxman S G
Department of Neurology, Yale University School of Medicine, New Haven Connecticut 06510, USA.
J Neurophysiol. 1998 Jul;80(1):196-208. doi: 10.1152/jn.1998.80.1.196.
N-methyl--aspartate (NMDA) receptor activation plays a fundamental role in the genesis of electrical activity of immature neurons and may participate in activity-dependent aspects of CNS development. A recent study has suggested that NMDA-receptor-mediated glutamatergic neurotransmission might occur in the developing spinal cord via activation of nonsynaptic receptors, but the details of NMDA-receptor activation in the developing CNS are not yet well understood. We describe here a model of cultured spinal neurons that display ongoing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activity characterized by spontaneous excitatory postsynaptic currents (EPSCs), with NMDA-receptor activity detectable only as single channel events. -2-amino-5-phosphonovaleric acid (100 microM) and tetrodotoxin (TTX) 100 nM each reduced the occurrence of spontaneous AMPA EPSCs; quantal analysis showed a decrease in the number of released quanta but no changes in quantal size, indicating that NMDA-receptor activation and Na+ channel activity affect the generation of spontaneous AMPA EPSCs, at least in part, via mechanisms that impinge on the presynaptic terminal. Once the Mg2+-block was released, activity of NMDA receptors dramatically increased the release of quantal and multiquantal amounts of glutamate, indicating that the NMDA receptors are physiologically coupled to glutamate release. In Mg2+-free solution, TTX application elicited an increase in the number of quantal AMPA EPSCs and a reduction in the number of multiquantal EPSCs, consistent with an effect of NMDA-receptor activation on presynaptic terminals. Our results suggest that endogenous activity at a small number of NMDA receptors can regulate the release of neurotransmitters at developing AMPA synapses.
N-甲基-D-天冬氨酸（NMDA）受体激活在未成熟神经元电活动的发生中起基本作用，并可能参与中枢神经系统发育中依赖活动的方面。最近的一项研究表明，NMDA受体介导的谷氨酸能神经传递可能通过非突触受体的激活在发育中的脊髓中发生，但发育中的中枢神经系统中NMDA受体激活的细节尚未得到很好的理解。我们在此描述了一种培养的脊髓神经元模型，该模型显示出持续的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体活性，其特征为自发性兴奋性突触后电流（EPSCs），而NMDA受体活性仅可检测为单通道事件。-2-氨基-5-磷酸戊酸（100微摩尔）和河豚毒素（TTX）100纳摩尔各自减少了自发性AMPA EPSCs的发生；量子分析显示释放的量子数量减少，但量子大小没有变化，表明NMDA受体激活和Na+通道活性至少部分地通过影响突触前终末的机制来影响自发性AMPA EPSCs的产生。一旦Mg2+阻断被解除，NMDA受体的活性会显著增加量子和多量子谷氨酸的释放，表明NMDA受体在生理上与谷氨酸释放偶联。在无Mg2+溶液中，应用TTX会引起量子AMPA EPSCs数量增加和多量子EPSCs数量减少，这与NMDA受体激活对突触前终末的作用一致。我们的结果表明，少数NMDA受体的内源性活性可以调节发育中的AMPA突触处神经递质的释放。
