Mg2+ block properties of triheteromeric GluN1-GluN2B-GluN2D NMDA receptors on neonatal rat substantia nigra pars compacta dopaminergic neurones.
Mg2+ block properties of triheteromeric GluN1-GluN2B-GluN2D NMDA receptors on neonatal rat substantia nigra pars compacta dopaminergic neurones.
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三异体 GluN1-GluN2B-GluN2D NMDA 受体对新生大鼠黑质致密部多巴胺能神经元的 Mg2 阻断特性
DOI：
10.1113/jphysiol.2013.267864
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发表时间：
2014-05-15
期刊：
影响因子：
--
通讯作者：
Gibb AJ
中科院分区：
文献类型：
--
作者：
Huang Z;Gibb AJ
天然NMDA受体（NMDAR）是由两个GluN 1和两个GluN 2亚基形成的四聚体通道。迄今为止，已经鉴定出7种NMDAR亚基，它们可以形成二异源聚体或三异源聚体NMDAR（不止一种类型的GluN 2亚基）。细胞外Mg ~（2+）是NMDARs的重要调节因子，尤其是Mg ~（2+）阻滞的电压依赖性对NMDARs在突触可塑性和突触活动与神经元活动整合中的作用至关重要。虽然二异源NMDAR的Mg 2+阻断性质已被充分研究，但三异源NMDAR的性质仍不清楚。我们以前的数据表明，多巴胺能神经元表达三异聚体GluN 1-GluN 2B-GluN 2D NMDAR。在这里，使用NMDARs在多巴胺能神经元从出生后第7天（P7）大鼠作为一个模型系统，我们的特点是电压依赖性镁块特性的三异源NMDARs。在对照条件下，外源性Mg 2+以电压依赖性方式显著抑制全细胞NMDA诱发电流，在−90 mV、−70 mV和−50 mV时的IC 50值分别为20.9 μm、53.3 μm和173 μm。当应用GluN 2B选择性拮抗剂ifenprodil时，残余NMDA介导的电流的Mg 2+敏感性降低，（主要由GluN 1-GluN 2B-GluN 2D NMDAR携带）降低至45.9 μm（−90 mV）、104 μm（−70 mV）和276 μm（−50 mV）的IC 50值，这表明三异聚体GluN 1-GluN 2B-GluN 2D NMDAR对外部Mg 2+的亲和力低于GluN 1-GluN 2B受体。此外，用捕获Mg 2+阻断模型拟合INMDA-V曲线显示，三异聚体GluN 1-GluN 2B-GluN 2D NMDAR比GluN 1-GluN 2B NMDAR具有更弱的电压依赖性Mg 2+阻断（δ = 0.56）。最后，我们的浓度跳跃和单通道记录表明，GluN 1-GluN 2B-GluN 2D而不是GluN 1-GluN 2D NMDAR存在。这些数据提供了与三异聚体NMDAR的Mg 2+阻断特征相关的信息，并可能有助于更好地理解依赖于这些三异聚体NMDAR的突触可塑性。
Native NMDA receptors (NMDARs) are tetrameric channels formed by two GluN1 and two GluN2 subunits. So far, seven NMDARs subunits have been identified and they can form diheteromeric or triheteromeric NMDARs (more than one type of GluN2 subunit). Extracellular Mg2+ is an important regulator of NMDARs, and particularly the voltage dependence of Mg2+ block is crucial to the roles of NMDARs in synaptic plasticity and the integration of synaptic activity with neuronal activity. Although the Mg2+ block properties of diheteromeric NMDARs are fully investigated, properties of triheteromeric NMDARs are still not clear. Our previous data suggested that dopaminergic neurones expressed triheteromeric GluN1–GluN2B–GluN2D NMDARs. Here, using NMDARs in dopaminergic neurones from postnatal day 7 (P7) rats as a model system, we characterize the voltage-dependent Mg2+ block properties of triheteromeric NMDARs. In control conditions, external Mg2+ significantly inhibits the whole cell NMDA-evoked current in a voltage-dependent manner with IC50 values of 20.9 μm, 53.3 μm and 173 μm at −90 mV, −70 mV and −50 mV, respectively. When the GluN2B-selective antagonist ifenprodil was applied, the Mg2+ sensitivity of the residual NMDA-mediated currents (which is mainly carried by GluN1–GluN2B–GluN2D NMDARs) is reduced to IC50 values of 45.9 μm (−90 mV), 104 μm (−70 mV) and 276 μm (−50 mV), suggesting that triheteromeric GluN1–GluN2B–GluN2D NMDARs have less affinity for external Mg2+ than GluN1–GluN2B receptors. In addition, fitting INMDA–V curves with a trapping Mg2+ block model shows the triheteromeric GluN1–GluN2B–GluN2D NMDARs have weaker voltage-dependent Mg2+ block (δ = 0.56) than GluN1–GluN2B NMDARs. Finally, our concentration jump and single channel recordings suggest that GluN1–GluN2B–GluN2D rather than GluN1–GluN2D NMDARs are present. These data provide information relevant to Mg2+ block characteristics of triheteromeric NMDARs and may help to better understand synaptic plasticity, which is dependent on these triheteromeric NMDARs.
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影响因子：
3.3
作者：
Martel, M. -A.;Wyllie, D. J. A.;Hardingham, G. E.
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