Bergles D E, Dzubay J A, Jahr C E
Vollum Institute L474, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201-3098, USA.
Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14821-5. doi: 10.1073/pnas.94.26.14821.
Glutamate transporters in the central nervous system are expressed in both neurons and glia, they mediate high affinity, electrogenic uptake of glutamate, and they are associated with an anion conductance that is stoichiometrically uncoupled from glutamate flux. Although a complete cycle of transport may require 50-100 ms, previous studies suggest that transporters can alter synaptic currents on a much faster time scale. We find that application of L-glutamate to outside-out patches from cerebellar Bergmann glia activates anion-potentiated glutamate transporter currents that activate in <1 ms, suggesting an efficient mechanism for the capture of extrasynaptic glutamate. Stimulation in the granule cell layer in cerebellar slices elicits all or none alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor and glutamate transporter currents in Bergmann glia that have a rapid onset, suggesting that glutamate released from climbing fiber terminals escapes synaptic clefts and reaches glial membranes shortly after release. Comparison of the concentration dependence of both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor and glutamate transporter kinetics in patches with the time course of climbing fiber-evoked responses indicates that the glutamate transient at Bergmann glial membranes reaches a lower concentration than attained in the synaptic cleft and remains elevated in the extrasynaptic space for many milliseconds.
中枢神经系统中的谷氨酸转运体在神经元和神经胶质细胞中均有表达,它们介导谷氨酸的高亲和力、生电摄取,并且与一种阴离子电导相关,该电导在化学计量上与谷氨酸通量解偶联。尽管完整的转运周期可能需要50 - 100毫秒,但先前的研究表明,转运体可以在更快的时间尺度上改变突触电流。我们发现,将L - 谷氨酸应用于小脑伯格曼神经胶质细胞的外翻片会激活阴离子增强的谷氨酸转运体电流,该电流在<1毫秒内激活,这表明存在一种捕获突触外谷氨酸的有效机制。小脑切片颗粒细胞层的刺激会在伯格曼神经胶质细胞中引发全或无的α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸受体和谷氨酸转运体电流,这些电流起始迅速,这表明从攀缘纤维终末释放的谷氨酸在释放后不久就会逸出突触间隙并到达神经胶质细胞膜。将外翻片中α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸受体和谷氨酸转运体动力学的浓度依赖性与攀缘纤维诱发反应的时间进程进行比较,结果表明伯格曼神经胶质细胞膜处的谷氨酸瞬变达到的浓度低于突触间隙中的浓度,并且在突触外空间中会持续升高许多毫秒。