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Reaction mechanism determines NMDA receptor response to repetitive stimulation

机译:反应机制决定NMDA受体对重复刺激的反应

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At central excitatory synapses, N-methyl-D-aspartate (NMDA) receptors, which have a high affinity for glutamate(1), produce a slowly rising synaptic current in response to a single transmitter pulse and an additional current after a second, closely timed stimulus(2). Here we show, by examining the kinetics of transmitter binding and channel gating in single-channel currents from recombinant NR1/NR2A receptors, that the synaptic response to trains of impulses is determined by the molecular reaction mechanism of the receptor. The rate constants estimated for the activation reaction predict that, after binding neurotransmitter, receptors hesitate for similar to4 ms in a closed high-affinity conformation before they either proceed towards opening or release neurotransmitter, with about equal probabilities. Because only about half of the initially fully occupied receptors become active, repetitive stimulation elicits currents with distinct waveforms depending on pulse frequency. This high-affinity/low-efficiency activation mechanism might serve as a link between stimulation frequency and the directionality of the ensuing synaptic plasticity.
机译:在中央兴奋性突触处,对谷氨酸(1)具有高亲和力的N-甲基-D-天冬氨酸(NMDA)受体产生缓慢上升的突触电流,以响应单个发射脉冲,并在第二个紧密闭合后产生额外电流。定时刺激(2)。在这里,我们显示,通过检查重组NR1 / NR2A受体在单通道电流中的递质结合和通道门控的动力学,对脉冲序列的突触反应是由受体的分子反应机制决定的。估计的激活反应速率常数预测,在结合神经递质后,受体在闭合的高亲和力构象下犹豫约4毫秒,然后开始打开或释放神经递质,概率大致相等。因为只有大约一半的最初完全占据的受体变得活跃,所以重复刺激会根据脉冲频率以不同的波形引发电流。这种高亲和力/低效率的激活机制可能充当刺激频率和随之而来的突触可塑性的方向性之间的联系。

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