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重组AMPA受体的单通道特性取决于RNA编辑、剪接变异和亚基组成。

Single-channel properties of recombinant AMPA receptors depend on RNA editing, splice variation, and subunit composition.

作者信息

Swanson G T, Kamboj S K, Cull-Candy S G

机构信息

Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom.

出版信息

J Neurosci. 1997 Jan 1;17(1):58-69. doi: 10.1523/JNEUROSCI.17-01-00058.1997.

DOI:10.1523/JNEUROSCI.17-01-00058.1997
PMID:8987736
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6793687/
Abstract

Non-NMDA glutamate receptor subunits of the AMPA-preferring subfamily combine to form ion channels with heterogeneous functional properties. We have investigated the effects of RNA editing at the Q/R site, splice variation of the "flip/flop" cassette, and multimeric subunit assembly on the single-channel conductance and kinetic properties of the recombinant AMPA receptors formed from GluR2 and GluR4 expressed in HEK 293 cells. We found that AMPA receptor single-channel conductance was dependent on the Q/R site editing state of the subunits comprising the channel. Calcium-permeable (unedited) channels had resolvable single-channel events with main conductance states of 7-8 pS, whereas fully edited GluR2 channels had very low conductances of approximately 300 fS (estimated from noise analysis). Additionally, the flip splice variant of GluR4 conferred agonist-dependent conductance properties reminiscent of those found for a subset of AMPA receptors in cultured cerebellar granule cells. These results provide a description of the single-channel properties of certain recombinant AMPA receptors and suggest that the single-channel conductance may be determined by the expression of edited GluR2 subunits in neurons.

摘要

AMPA 偏好亚家族的非 NMDA 谷氨酸受体亚基组合形成具有异质功能特性的离子通道。我们研究了 Q/R 位点的 RNA 编辑、“翻转/翻转”盒的剪接变异以及多聚体亚基组装对在 HEK 293 细胞中表达的由 GluR2 和 GluR4 形成的重组 AMPA 受体单通道电导和动力学特性的影响。我们发现,AMPA 受体单通道电导取决于构成通道的亚基的 Q/R 位点编辑状态。钙通透(未编辑)通道具有可分辨的单通道事件,主要电导状态为 7 - 8 pS,而完全编辑的 GluR2 通道电导非常低,约为 300 fS(通过噪声分析估计)。此外,GluR4 的翻转剪接变体赋予了激动剂依赖性电导特性,这让人联想到在培养的小脑颗粒细胞中一部分 AMPA 受体的特性。这些结果描述了某些重组 AMPA 受体的单通道特性,并表明单通道电导可能由神经元中编辑后的 GluR2 亚基的表达所决定。

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AMPA receptor heterogeneity in rat hippocampal neurons revealed by differential sensitivity to cyclothiazide.通过对环噻嗪的不同敏感性揭示大鼠海马神经元中的AMPA受体异质性
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