Elevation of intradendritic sodium concentration mediated by synaptic activation of metabotropic glutamate receptors in cerebellar Purkinje cells
Elevation of intradendritic sodium concentration mediated by synaptic activation of metabotropic glutamate receptors in cerebellar Purkinje cells
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DOI：
10.1046/j.1460-9568.2000.00122.x
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发表时间：
2000-06-01
影响因子：
3.4
通讯作者：
Strata, P
中科院分区：
文献类型：
--
作者：
Knöpfel, T;Anchisi, D;Strata, P
小脑浦肯野细胞表达离子型谷氨酸受体和代谢型谷氨酸受体。短暂强直刺激大鼠和小鼠小脑切片中的平行纤维，在浦肯野细胞中引起由代谢型谷氨酸受体mGluR（1）亚型介导的缓慢兴奋性突触后电流。这种mGluR（1）EPSC的效应系统尚未确定。在本研究中，我们使用全细胞膜片钳技术结合荧光钠指示剂SBFI对细胞内钠浓度（[Na+]（i））的显微荧光记录来记录mGluR 1 EPSC。在离子型谷氨酸受体拮抗剂NBQX和D-APV以及GABA（A）受体拮抗剂荷包牡丹碱或印防己毒素存在下，通过局部平行刺激纤维诱导mGluR（1）EPSC。mGluR 1 EPSC与[Na+]（i）增加相关，仅限于树突树的特定部分。mGluR拮抗剂S-MCPG可抑制mGluR（1）EPSC和[Na+]（i）的增加。在NBQX、D-APV、苦味酸毒素和TTX的存在下，选择性mGluR激动剂3，5-DHPG的浴应用诱导[Na+]i的升高，其延伸到浦肯野细胞的整个树突区域。这一发现表明，mGluR（1）介导的突触后电流导致大量钠离子流入浦肯野细胞的树突状细胞质，从而提供了一种新的细胞内信号传导机制，可能涉及该突触的mGluR（1）依赖性突触可塑性。
Cerebellar Purkinje cells express both ionotropic glutamate receptors and metabotropic glutamate receptors. Brief tetanic stimulation of parallel fibers in rat and mouse cerebellar slices evokes a slow excitatory postsynaptic current in Purkinje cells that is mediated by the mGluR(1) subtype of metabotropic glutamate receptors. The effector system underlying this mGluR(1) EPSC has not yet been identified. In the present study, we recorded the mGluR1 EPSC using the whole-cell patch-clamp technique in combination with microfluorometric recordings of the intracellular sodium concentration ([Na+](i)) by means of the fluorescent sodium indicator SBFI. The mGluR(1) EPSC was induced by local parallel fibre stimulation in the presence of the ionotropic glutamate receptor antagonists NBQX and D-APV and the GABA(A) receptor antagonists bicuculline or picrotoxin. The mGluR1 EPSC was associated with an increase in [Na+](i) that was restricted to a specific portion of the dendritic tree. The mGluR(1) EPSC as well as the increase in [Na+](i) were inhibited by the mGluR antagonist S-MCPG. In the presence of NBQX, D-APV, pictrotoxin and TTX, bath application of the selective mGluR agonist 3,5-DHPG induced an elevation in [Na+]i which extended over the whole dendritic field of the Purkinje Cell. This finding demonstrates that the mGluR(1)-mediated postsynaptic current leads to a significant influx of sodium into the dendritic cytoplasm of Purkinje cells and thereby provides a novel intracellular signalling mechanism that might be involved in mGluR(1)-dependent synaptic plasticity at this synapse.