Synaptically released glutamate does not overwhelm transporters on hippocampal astrocytes during high-frequency stimulation
Synaptically released glutamate does not overwhelm transporters on hippocampal astrocytes during high-frequency stimulation
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DOI：
10.1152/jn.2000.83.5.2835
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发表时间：
2000-05-01
影响因子：
2.5
通讯作者：
Jahr, CE
中科院分区：
文献类型：
--
作者：
Diamond, JS;Jahr, CE
除了将细胞外谷氨酸浓度维持在低环境水平外，高亲和力谷氨酸转运蛋白通过加速谷氨酸从突触间隙的清除并限制突触之间递质溢出的程度而在突触传递中发挥直接作用。转运蛋白在神经元和神经胶质中都有表达，但神经胶质转运蛋白可能在从细胞外间隙清除突触释放的谷氨酸中起主要作用。通过测量神经元和星形胶质细胞中突触激活的转运蛋白介导的电流（STC），直接研究了转运蛋白在突触传递中的作用。在这里，我们记录从星形胶质细胞在海马切片的CA1区，并引发STC与高频（100 Hz）的刺激列车的不同长度，以确定是否运输不堪重负的刺激，诱导长时程增强。我们发现，在接近生理温度（34摄氏度），高频刺激（HFS）不影响转运蛋白清除突触外空间谷氨酸的速率。因此，虽然在“正常”刺激期间突触之间的溢出可能会损害快速兴奋性突触传递的绝对突触特异性，但溢出在HFS期间不会加剧。在室温（24 ℃）下，转运蛋白的能力有所降低，尽管在短暂的“θ爆发”刺激期间释放的递质仍然像单一刺激后一样迅速清除，即使在通过药理学手段部分降低转运能力时也是如此。
In addition to maintaining the extracellular glutamate concentration at low ambient levels, high-affinity glutamate transporters play a direct role in synaptic transmission by speeding the clearance of glutamate from the synaptic cleft and limiting the extent to which transmitter spills over between synapses. Transporters are expressed in both neurons and glia, but glial transporters are likely to play the major role in removing synaptically released glutamate from the extracellular space. The role of transporters in synaptic transmission has been studied directly by measuring synaptically activated, transporter-mediated currents (STCs) in neurons and astrocytes. Here we record from astrocytes in the CA1 region of hippocampal slices and elicit STCs with high-frequency (100 Hz) stimulus trains of varying length to determine whether transporters are overwhelmed by stimuli that induce long-term potentiation. We show that, at near-physiological temperatures (34 degrees C), high-frequency stimulation (HFS) does not affect the rate at which transporters clear glutamate from the extrasynaptic space. Thus, although spillover between synapses during "normal" stimulation may compromise the absolute synapse specificity of fast excitatory synaptic transmission, spillover is not exacerbated during HFS. Transporter capacity is diminished somewhat at room temperature (24 degrees C), although transmitter released during brief, "theta burst" stimulation is still cleared as quickly as following a single stimulus, even when transport capacity is partially diminished by pharmacological means.