Sodium signals in cerebellar Purkinje neurons and Bergmann glial cells evoked by glutamatergic synaptic transmission
Sodium signals in cerebellar Purkinje neurons and Bergmann glial cells evoked by glutamatergic synaptic transmission
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DOI：
10.1002/glia.20685
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发表时间：
2008-08-01
期刊：
影响因子：
6.2
通讯作者：
Rose, Christine R.
中科院分区：
文献类型：
--
作者：
Bennay, Mustapha;Langer, Julia;Rose, Christine R.
神经胶质细胞表达谷氨酸的特异性高亲和力转运蛋白，其在大脑兴奋性突触的谷氨酸清除中发挥核心作用。这些转运蛋白是产电的，主要由钠的电化学梯度供能。在本研究中，我们结合体细胞全细胞膜片钳记录与定量Na+成像在小脑Bergmann神经胶质细胞的细细胞分支和浦肯野神经元的树突分析细胞内Na+信号接近激活的突触。我们表明，压力应用谷氨酸盐和谷氨酸盐激动剂导致局部Na+信号在mM范围内。此外，我们分析了药理学概况，以及Na+信号的时间过程和空间分布后，短的突触爆发刺激的平行或攀爬纤维。虽然平行纤维刺激导致局部钠瞬变，在接近刺激移液管的过程中是最大的，攀爬纤维刺激引起整个细胞的全局钠瞬变。神经胶质细胞钠信号达几mM，主要是由谷氨酸内向运输后的钠内流引起的，并持续数十秒。相反，浦肯野神经元树突中的钠瞬变主要由AMPA受体的激活引起，并且具有快得多的动力学。通过减少钠依赖性谷氨酸摄取的驱动力，神经胶质细胞在重复活动时的细胞内钠积累可能提供负反馈机制，促进谷氨酸的扩散和小脑活动突触处突触外谷氨酸受体的激活。(c)2008 Wiley-Liss，Inc.
Glial cells express specific high-affinity transporters for glutamate that play a central role in glutamate clearance at excitatory synapses in the brain. These transporters are electrogenic and are mainly energized by the electrochemical gradient for sodium. In the present study, we combined somatic whole-cell patch-clamp recordings with quantitative Na+ imaging in fine cellular branches of cerebellar Bergmann glial cells and in dendrites of Purkinje neurons to analyze intracellular Na+ signals close to activated synapses. We demonstrate that pressure application of glutamate and glutamate agonists causes local Na+ signals in the mM range. Furthermore, we analyzed the pharmacological profile, as well as the time course and spatial distribution of Na+ signals following short synaptic burst stimulation of parallel or climbing fibers. While parallel fibers stimulation resulted in local sodium transients that were largest in processes close to the stimulation pipette, climbing fibers stimulation elicited global sodium transients throughout the entire cell. Glial sodium signals amounted to several mM, were mainly caused by sodium influx following inward transport of glutamate and persisted for tens of seconds. Sodium transients in dendrites of Purkinje neurons, in contrast, were mainly caused by activation of AMPA receptors and had much faster kinetics. By reducing the driving force for sodium-dependent glutamate uptake, intracellular sodium accumulation in glial cells upon repetitive activity might provide a negative feedback mechanism, promoting the diffusion of glutamate and the activation of extrasynaptic glutamate receptors at active synapses in the cerebellum. (c) 2008 Wiley-Liss, Inc.