SDF-1α-mediated modulation of synaptic transmission in rat cerebellum
SDF-1α-mediated modulation of synaptic transmission in rat cerebellum
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DOI：
10.1046/j.1460-9568.2000.00139.x
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发表时间：
2000-07-01
影响因子：
3.4
通讯作者：
Eusebi, F
中科院分区：
文献类型：
--
作者：
Limatola, C;Giovannelli, A;Eusebi, F
通过用多克隆抗CXCR-4 Ab染色，并通过评估培养的小脑颗粒细胞和小脑切片中的浦肯野神经元（PN）中对生理激动剂基质衍生细胞因子-1 α（SDF-1 α）的钙反应，证明了大鼠神经细胞中七跨膜结构域G蛋白偶联趋化因子受体CXCR-4/融合素的功能表达。小脑神经胶质细胞、颗粒细胞和浦肯野细胞显示出CXCR-4的显著染色。此外，培养的颗粒细胞表现出Ca 2+瞬变引起的SDF-1 α的应用，无论是在细胞体和神经元的过程。小脑切片中的全细胞膜片钳PNs通过缓慢的内向电流对SDF-1 α的应用作出反应，随后细胞内Ca 2+水平和自发突触活动均增加。特别是，SDF-1 α诱导的缓慢内向电流大大减少离子型谷氨酸受体阻滞剂，但在介质中，突触传递被抑制，表明该电流可能是，至少部分，介导的突触外谷氨酸，可能从周围的神经胶质细胞和/或神经细胞释放的充分发展。总之，这些发现表明CXCR-4在突触传递的调节中的功能参与，为在小脑中发挥神经调节作用的趋化因子受体的库增加了另一个成员。
The functional expression of the seven-transmembrane domain G protein-coupled chemokine receptor CXCR-4/fusin in rat nerve cell was demonstrated by staining with a polyclonal anti-CXCR-4 Ab, and by evaluating the calcium responses to the physiological agonist stromal-derived cell factor-1 alpha (SDF-1 alpha) in both cerebellar granule cells in culture and Purkinje neurons (PNs) in cerebellar slices. Cerebellar glial, granule and Purkinje cells showed a pronounced staining for CXCR-4. Furthermore, cultured granule cells exhibited Ca2+ transients elicited by the application of SDF-1 alpha, both in cell bodies and in neuronal processes. Whole-cell patch-clamped PNs in cerebellar slices responded to SDF-1 alpha application by a slow inward current followed by an increase of both intracellular Ca2+ level and spontaneous synaptic activity. In particular, the SDF-1 alpha-induced slow inward current was considerably reduced by ionotropic glutamate receptor blockers, but developed fully in a medium in which synaptic transmission was inhibited, indicating that this current might be, at least in part, mediated by extrasynaptic glutamate, possibly released from the surrounding glial and/or nerve cells. Taken together, these findings indicate a functional involvement of CXCR-4 in the modulation of synaptic transmission, adding another member to the repertoire of the chemokine receptors exerting a neuromodulatory role in the cerebellum.