Delayed clearance of transmitter and the role of glutamate transporters at synapses with multiple release sites
Delayed clearance of transmitter and the role of glutamate transporters at synapses with multiple release sites
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DOI：
10.1523/jneurosci.16-05-01634.1996
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发表时间：
1996-03-01
影响因子：
5.3
通讯作者：
Trussell, LO
中科院分区：
文献类型：
--
作者：
Otis, TS;Wu, YC;Trussell, LO
在肾盏突触处检查了谷氨酸扩散、摄取和通道动力学在形成 AMPA 受体 EPSC 中的作用。 EPSC 衰减由三个指数分量描述：两个匹配的脱敏通道动力学，以及至少慢 10 倍的第三个分量。最慢的成分与稳态 AMPA 电流具有相同的电压依赖性，并且通过谷氨酸摄取的阻断而选择性地增加和延长，表明缓慢的 EPSC 代表谷氨酸在部分脱敏的 AMPA 受体上的重新结合。这些数据与递质从多个释放位点扩散到大突触间隙的模型的预测非常一致。在释放后的第一毫秒内，裂隙中的递质浓度降至毫摩尔水平以下，导致 EPSC 最快的部分由通道动力学形成。最慢的成分是通过扩散和吸收在数十毫秒内去除最终的 10-100 μM 谷氨酸来确定的。数据和模型表明，递质的摄取和释放位点之间的合作是突触间隙中谷氨酸缓慢“尾部”的重要决定因素。谷氨酸的缓慢清除可能会通过脱敏来限制突触后受体的可用性。
The roles of glutamate diffusion, uptake, and channel kinetics in shaping the AMPA receptor EPSC were examined at a calyceal synapse. The EPSC decay was described by three exponential components: two matching desensitizing channel kinetics, and a third component at least 10 times slower. The slowest component had identical voltage dependence to the steady-state AMPA current and was selectively increased and prolonged by blockade of glutamate uptake, indicating that the slow EPSC represented rebinding of glutamate at partially desensitized AMPA receptors, The data were in strong agreement with the predictions of a model of transmitter diffusion from multiple release sites into a large synaptic cleft. Within the first millisecond after release, transmitter concentrations in the cleft fell below millimolar levels, causing the fastest parts of the EPSC to be shaped by channel kinetics. The slowest component was determined by the removal over tens of milliseconds of the final 10-100 mu M glutamate by diffusion and uptake. The data and modeling indicate that transmitter uptake and cooperation between release sites are significant determinants of a slow ''tail'' of glutamate in the synaptic cleft. This slow clearance of glutamate is likely to limit postsynaptic receptor availability through desensitization.