Extrasynaptic and synaptic and uniform pools in rat hi NMDA receptors form stable ppocampal slices

Extrasynaptic and synaptic and uniform pools in rat hi NMDA receptors form stable ppocampal slices
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DOI:
10.1113/jphysiol.2007.137679
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发表时间:
2007-10-15
影响因子:
5.5
通讯作者:
Pettit, Diana L.
Pettit, Diana L.
中科院分区:
医学1区
文献类型:
--
作者:
Harris, Alexander Z.;Pettit, Diana L.

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N-甲基-D-天冬氨酸受体(NMDAR)激活可以触发长期和短期可塑性,促进细胞存活,并启动细胞死亡。许多研究表明,NMDAR激活的后果可能会有很大差异,具体取决于突触或突触外受体是否被激活。在这里,我们研究了急性解剖海马脑片CAI锥体神经元的NMDAR的空间分布。使用突触外受体的生理定义为那些无法访问的单一释放事件,我们发现,突触外NMDAR包括相当大的比例的树突状NMDAR池(36%)。这种突触外NMDAR池是稳定的,不会穿梭进入突触受体池,因为我们观察到MK-801突触阻断和洗脱后突触电流没有恢复。突触和突触外NMDA受体池的亚基组成在3周龄时是相似的,NR 213亚基存在于两个隔室中。NR 213受体在突触外区室中不富集。我们的数据表明,突触外NMDAR在突触传递中所起的任何作用都是由它们的亚细胞位置决定的,而不是它们的亚基组成(或移动性)。
N-methyl-D-aspartate receptor (NMDAR) activation can trigger both long- and short-term plasticity, promote cell survival, and initiate cell death. A number of studies suggest that the consequences of NMDAR activation can vary widely depending on whether synaptic or extrasynaptic receptors are activated. Here we have examined the spatial distribution of NMDARs of CAI pyramidal neurons in acutely dissected hippocampal slices. Using a physiological definition of extrasynaptic receptors as those not accessible to single release events, we find that extrasynaptic NMDARs comprise a substantial proportion of the dendritic NMDAR pool (36%). This pool of extrasynaplic NMDARs is stable and does not shuttle into the synaptic receptor pool, as we observe no recovery of synaptic current after MK-801 synaptic blockade and washout. The subunit composition of synaptic and extrasynaptic NMDA receptor pools is similar at 3 weeks of age, with NR213 subunits present in both compartments. NR213 receptors are not enriched in the extrasynaptic compartment. Our data suggest that any role played by extrasynaptic NMDARs in synaptic transmission is dictated by their subcellular location rather than their subunit composition (or mobility.