Liu Siqiong June, Cull-Candy Stuart G
Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom.
J Neurosci. 2002 May 15;22(10):3881-9. doi: 10.1523/JNEUROSCI.22-10-03881.2002.
High-frequency synaptic stimulation is thought to cause a rapid and lasting change in the expression of GluR2 subunit-containing AMPA receptors (AMPARs) at synapses in cerebellar stellate cells. We examined whether spontaneous synaptic activity affects the expression of GluR2-containing synaptic AMPARs and whether the change in AMPAR subtypes alters their Ca(2+) permeability and kinetic properties. We used intracellular spermine, which blocks GluR2-lacking receptors at depolarized potentials, to distinguish the presence of GluR2. In most cells, the spontaneous EPSC frequency was low, and evoked EPSCs displayed inwardly rectifying I-V relationships, indicative of the presence of GluR2-lacking AMPARs. However, in cells that displayed a higher rate of spontaneous synaptic activity, EPSCs gave linear I-V plots, suggesting the presence of GluR2-containingAMPARs. This is consistent with the idea that spontaneous synaptic activity increased the expression of GluR2-containing AMPARs at synapses. The Ca(2+) permeability of AMPARs that gave inwardly rectifying currents in outside-out patches from TTX-treated cells was six times higher than in control cells that gave linear or outwardly rectifying I-V plots. However, increased spontaneous synaptic activity did not significantly alter the EPSC decay time. Furthermore, the decay time course ofEPSCs mediated by GluR2-containing receptors was not different from that mediated by a mixed population of receptors at the same synapse. Our results suggest that the level of spontaneous synaptic activity can determine the subunit composition of postsynaptic receptors at this synapse. The activity-induced expression of GluR2-containing receptors significantly reduced the Ca(2+) permeability of AMPARs in stellate cells but did not slow the decay time course of synaptic currents.
高频突触刺激被认为会导致小脑星状细胞突触处含GluR2亚基的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPARs）的表达发生快速且持久的变化。我们研究了自发突触活动是否会影响含GluR2的突触AMPARs的表达，以及AMPAR亚型的变化是否会改变其Ca(2+)通透性和动力学特性。我们使用细胞内精胺，其在去极化电位下阻断缺乏GluR2的受体，以区分GluR2的存在。在大多数细胞中，自发兴奋性突触后电流（EPSC）频率较低，诱发的EPSC呈现内向整流的电流-电压（I-V）关系，表明存在缺乏GluR2的AMPARs。然而，在自发突触活动速率较高的细胞中，EPSC给出线性I-V图，表明存在含GluR2的AMPARs。这与自发突触活动增加突触处含GluR2的AMPARs表达的观点一致。在来自经河豚毒素（TTX）处理的细胞的外翻片膜中产生内向整流电流的AMPARs的Ca(2+)通透性比给出线性或外向整流I-V图的对照细胞高六倍。然而，自发突触活动增加并未显著改变EPSC衰减时间。此外，由含GluR2的受体介导的EPSC的衰减时间进程与同一突触处由混合受体群体介导的EPSC衰减时间进程没有差异。我们的结果表明，自发突触活动水平可以决定该突触处突触后受体的亚基组成。活动诱导的含GluR2的受体表达显著降低了星状细胞中AMPARs的Ca(2+)通透性，但并未减缓突触电流的衰减时间进程。
