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钙通透性和非通透性 AMPA 受体在鲤鱼视网膜水平细胞上的突触贡献及其被锌的调制。

Synaptic contribution of Ca2+-permeable and Ca2+-impermeable AMPA receptors on isolated carp retinal horizontal cells and their modulation by Zn2+.

机构信息

School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong-Chuan Road, Shanghai 200240, China.

出版信息

Brain Res. 2010 Mar 4;1317:60-8. doi: 10.1016/j.brainres.2009.12.068. Epub 2010 Jan 4.

Abstract

Ca(2+)-permeable and Ca(2+)-impermeable AMPA receptors are co-expressed on carp retinal horizontal cells. In the present study, we examined the synaptic contribution and Zn(2+) modulatory effect of these two AMPA receptor subtypes using whole-cell patch clamp technique. Specific Ca(2+)-permeable AMPA receptor antagonist (1-naphthyl acetyl spermine, NAS) and selective Ca(2+)-impermeable AMPA receptor blocker (pentobarbital, PB) were used to separate the glutamate-response in isolated H1 horizontal cell mediated by these two subtypes of AMPA receptors respectively. Application of 100 microM NAS substantially suppressed the current elicited by 3 mM glutamate and the remaining NAS-insensitive component was completely blocked by application of 100 microM PB. In addition, Zn(2+) had dual effects on Ca(2+)-permeable AMPA receptor-mediated current: at low concentration (10 microM), Zn(2+) potentiated the current, but at higher concentrations (100 and 1000 microM), Zn(2+) reduced the current in a dose-dependent manner. However, Zn(2+) (10, 100 and 1000 microM) failed to modulate the NAS-insensitive current mediated by Ca(2+)-impermeable AMPA receptors. Overall, our results suggest that Ca(2+)-permeable AMPA receptors contribute more to the cell's glutamate-response than Ca(2+)-impermeable AMPA receptors. Furthermore, Zn(2+) has dual effects on the Ca(2+)-permeable AMPA receptor activity without affecting Ca(2+)-impermeable AMPA receptors.

摘要

钙通透性和非通透性 AMPA 受体在鲤鱼视网膜水平细胞上共存。在本研究中,我们使用全细胞膜片钳技术研究了这两种 AMPA 受体亚型的突触贡献和 Zn2+调节作用。使用特定的钙通透性 AMPA 受体拮抗剂(1-萘乙酰基 spermine,NAS)和选择性的钙非通透性 AMPA 受体阻断剂(戊巴比妥,PB)分别分离由这两种 AMPA 受体亚型介导的分离 H1 水平细胞中的谷氨酸反应。应用 100 μM NAS 可显著抑制 3 mM 谷氨酸引起的电流,而剩余的 NAS 不敏感成分完全被 100 μM PB 阻断。此外,Zn2+对钙通透性 AMPA 受体介导的电流具有双重作用:在低浓度(10 μM)下,Zn2+增强电流,但在较高浓度(100 和 1000 μM)下,Zn2+以剂量依赖性方式减少电流。然而,Zn2+(10、100 和 1000 μM)未能调节由钙非通透性 AMPA 受体介导的 NAS 不敏感电流。总的来说,我们的结果表明,钙通透性 AMPA 受体比钙非通透性 AMPA 受体对细胞的谷氨酸反应贡献更大。此外,Zn2+对钙通透性 AMPA 受体活性具有双重作用,而不影响钙非通透性 AMPA 受体。

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