The activation mechanism of α1 homomeric glycine receptors
The activation mechanism of α1 homomeric glycine receptors
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DOI：
10.1523/jneurosci.4420-03.2004
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发表时间：
2004-01-28
影响因子：
5.3
通讯作者：
Sivilotti, LG
中科院分区：
文献类型：
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作者：
Beato, M;Groot-Kormelink, PJ;Sivilotti, LG
甘氨酸受体介导脊髓和脑干的快速突触抑制。它的激活机制尚不清楚，尽管这种受体在生理上很重要，而且它可以作为其他同戊二胺通道的原型。我们分析了大鼠重组α 1甘氨酸受体的单通道记录，同时将不同的机制拟合到四种甘氨酸浓度（10-1000 muM）下的一组开口序列。由此拟合的机制和速率常数的充分性是通过检查它们如何很好地描述观察到的停留时间分布、开闭相关性和单通道p -开剂量-反应曲线来判断的。我们发现，随着更多的甘氨酸分子结合到通道上，门控效应会增加，但当只有3个（5个）潜在结合位点被占据时，门控效应达到最大。连续的结合步骤并不相同，这意味着当通道关闭时，结合位点可以相互作用。这些相互作用可以根据同戊体内结合位点的拓扑结构来解释。
The glycine receptor mediates fast synaptic inhibition in the spinal cord and brainstem. Its activation mechanism is not known, despite the physiological importance of this receptor and the fact that it can serve as a prototype for other homopentameric channels. We analyzed single-channel recordings from rat recombinant alpha1 glycine receptors by fitting different mechanisms simultaneously to sets of sequences of openings at four glycine concentrations (10-1000 muM). The adequacy of the mechanism and the rate constants thus fitted was judged by examining how well these described the observed dwell-time distributions, open-shut correlation, and single-channel P-open dose-response curve. We found that gating efficacy increased as more glycine molecules bind to the channel, but maximum efficacy was reached when only three (of five) potential binding sites are occupied. Successive binding steps are not identical, implying that binding sites can interact while the channel is shut. These interactions can be interpreted in the light of the topology of the binding sites within a homopentamer.