Fast NMDA receptor-mediated synaptic currents in neurons from mice lacking the epsilon2 (NR2B) subunit.
Fast NMDA receptor-mediated synaptic currents in neurons from mice lacking the epsilon2 (NR2B) subunit.
复制标题
缺乏 epsilon2 (NR2B) 亚基的小鼠神经元中 NMDA 受体介导的快速突触电流。
DOI：
10.1152/jn.2000.83.1.616
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Westbrook,GL
中科院分区：
文献类型：
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作者：
Tovar,KR;Sprouffske,K;Westbrook,GL
n -甲基-d-天冬氨酸（NMDA）受体与突触连接的形成有关。为了研究在发育早期显著表达的ε2 (NR2B) NMDA受体亚基的作用，我们使用了缺乏该亚基的小鼠神经元。尽管ε2−/−小鼠在出生后很快死亡，我们通过拯救这些小鼠的海马神经元并在自适应培养中研究它们，来检验靶向突触后膜的NMDA受体是否依赖于ε2亚基。在电压钳记录中，来自ε2−/−神经元的兴奋性突触后电流（EPSCs）表达了NMDA受体介导的EPSC，这种EPSC在突触活动发展时就很明显。然而，与野生型神经元相比，NMDA受体介导的EPSC失活动力学要快得多，对甘氨酸的敏感性较低，但被Mg2+或AP5阻断。与野生型电流相比，来自ε2−/−神经元的全细胞电流对低浓度Zn2+的阻断更敏感，而对ε2特异性拮抗剂伊芬普罗地尔的敏感性要低得多。NMDA受体介导的EPSC快速失活动力学和ε2−/−神经元的药理学特征与缺乏ε2亚基的小鼠兴奋性海马神经元中ζ1/ε1二异聚体受体的表达一致。因此，ε1可以代替突触上的ε2亚基，而ε2不需要NMDA受体靶向突触后膜。
TheN-methyl-d-aspartate (NMDA) receptor has been implicated in the formation of synaptic connections. To investigate the role of the ε2 (NR2B) NMDA receptor subunit, which is prominently expressed during early development, we used neurons from mice lacking this subunit. Although ε2−/−mice die soon after birth, we examined whether NMDA receptor targeting to the postsynaptic membrane was dependent on the ε2 subunit by rescuing hippocampal neurons from these mice and studying them in autaptic cultures. In voltage-clamp recordings, excitatory postsynaptic currents (EPSCs) from ε2−/−neurons expressed an NMDA receptor–mediated EPSC that was apparent as soon as synaptic activity developed. However, compared with wild-type neurons, NMDA receptor–mediated EPSC deactivation kinetics were much faster and were less sensitive to glycine, but were blocked by Mg2+or AP5. Whole cell currents from ε2−/−neurons were also more sensitive to block by low concentrations of Zn2+and much less sensitive to the ε2-specific antagonist ifenprodil than wild-type currents. The rapid NMDA receptor–mediated EPSC deactivation kinetics and the pharmacological profile from ε2−/−neurons are consistent with the expression of ζ1/ε1 diheteromeric receptors in excitatory hippocampal neurons from mice lacking the ε2 subunit. Thus ε1 can substitute for the ε2 subunit at synapses and ε2 is not required for targeting of NMDA receptors to the postsynaptic membrane.