Deriving the glutamate clearance time course from transporter currents in CA1 hippocampal astrocytes: Transmitter uptake gets faster during development
Deriving the glutamate clearance time course from transporter currents in CA1 hippocampal astrocytes: Transmitter uptake gets faster during development
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DOI：
10.1523/jneurosci.5125-04.2005
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发表时间：
2005-03-16
影响因子：
5.3
通讯作者：
Diamond, JS
中科院分区：
文献类型：
--
作者：
Diamond, JS
在许多兴奋性突触中，神经递质谷氨酸扩散到突触间隙之外以激活突触外靶点。这种递质“溢出”对神经元网络处理能力的程度和影响尚不清楚，部分原因是尚不清楚递质在被高亲和力谷氨酸转运蛋白从细胞外空间去除之前从其释放点扩散多远。在海马星形胶质细胞中记录的突触激活的转运蛋白介导的电流（STC）提供了谷氨酸摄取的实验测量，但STC的时间过程可能被其他因素塑造或“过滤”，因此不能直接指示清除率。在这里，STC记录从星形胶质细胞在大鼠海马切片的条件下，其中摄取能力降低和STC衰减反映了谷氨酸清除率减慢。从这些响应中提取过滤机制的时间特性，并推导出控制条件下的谷氨酸清除时间过程。结果表明，谷氨酸可以清除突触外空间在1毫秒内。清除是最快的成人neurologic，相应的神经胶质转运蛋白表达的发展增加。突触释放的谷氨酸以与通过闪光光解释放的谷氨酸相同的速率被吸收，这表明转运蛋白相对于谷氨酸释放位点的空间位置不影响清除的时间过程。在年轻的动物中，较慢的清除率将允许谷氨酸扩散更远的距离，表明突触外受体在发育早期起着特别重要的作用。
At many excitatory synapses, the neurotransmitter glutamate diffuses beyond the synaptic cleft to activate extrasynaptic targets. The extent and impact of such transmitter "spillover" on the processing capacity of neuronal networks are unclear, in part because it remains unknown how far transmitter diffuses from its point of release before being removed from the extracellular space by high-affinity glutamate transporters. Synaptically activated, transporter-mediated currents (STCs) recorded in hippocampal astrocytes provide an experimental measure of glutamate uptake, but the time course of the STC may be shaped, or "filtered," by other factors and therefore not represent a direct indication of clearance rate. Here, STCs were recorded from astrocytes in rat hippocampal slices under conditions in which uptake capacity was reduced and the STC decay reflected a slowed rate of glutamate clearance. The temporal characteristics of the filtering mechanisms were extracted from these responses, and the glutamate clearance time course in control conditions was derived. The results indicate that glutamate can be cleared from the extrasynaptic space within 1 ms. Clearance is fastest in adult neuropil, corresponding to a developmental increase in glial transporter expression. Synaptically released glutamate is taken up at the same rate as glutamate released via flash photolysis, indicating that the spatial location of transporters relative to the site of glutamate release does not affect the time course of clearance. Slower clearance in young animals would permit glutamate to diffuse greater distances, indicating a particularly important role for extrasynaptic receptors early in development.