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多胺介导的离子通道阻断产生的AMPA和海人藻酸亚型谷氨酸受体的内向整流。

Inward rectification of both AMPA and kainate subtype glutamate receptors generated by polyamine-mediated ion channel block.

作者信息

Bowie D, Mayer M L

机构信息

Laboratory of Cellular and Molecular Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.

出版信息

Neuron. 1995 Aug;15(2):453-62. doi: 10.1016/0896-6273(95)90049-7.

Abstract

CA2+-permeable glutamate receptors assembled from subunits containing a GLN residue at the RNA editing site in membrane domain 2 show strong inward rectification. In HEK 293 cells transfected with the kainate receptor subunit GluR6(Q), inward rectification is lost in outside-out patches, suggesting a role for diffusible, cytoplasmic factors. Inclusion of different polyamines in the internal solution restored inward rectification, whereas Mg2+ (1 mM) was inactive. Spermidine (Kd[0 mV] = 5.5 microM) was of higher affinity than spermidine (Kd[0 mV] = 25.4 microM) or putrescine (Kd[0 mV] = 1.2 mM). AMPA receptors assembled from GluRA(flip) showed even higher affinity for spermine (Kd[0 mV] = 1.5 microM). Analysis of the voltage dependence of whole-cell responses predicted intracellular free spermine and spermidine concentrations of 51 and 153 muM, respectively.

摘要

由在膜结构域2的RNA编辑位点含有谷氨酰胺(GLN)残基的亚基组装而成的钙离子(Ca2+)通透型谷氨酸受体表现出强烈的内向整流。在用红藻氨酸受体亚基GluR6(Q)转染的人胚肾293(HEK 293)细胞中,外向膜片钳记录中内向整流消失,提示可扩散的胞质因子起作用。在内液中加入不同的多胺可恢复内向整流,而镁离子(Mg2+,1 mM)无此作用。亚精胺(Kd[0 mV]=5.5 microM)的亲和力高于精胺(Kd[0 mV]=25.4 microM)或腐胺(Kd[0 mV]=1.2 mM)。由GluRA(flip)组装而成的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体对精胺的亲和力更高(Kd[0 mV]=1.5 microM)。对全细胞反应的电压依赖性分析预测细胞内游离精胺和亚精胺浓度分别为51和153 microM。

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