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快速突触处突触小泡融合的单钙通道结构域门控;通过图形建模进行分析。

Single calcium channel domain gating of synaptic vesicle fusion at fast synapses; analysis by graphic modeling.

作者信息

Stanley Elise F

机构信息

a Toronto Western Research Institute ; Toronto , Ontario Canada.

出版信息

Channels (Austin). 2015;9(5):324-33. doi: 10.1080/19336950.2015.1098793.

Abstract

At fast-transmitting presynaptic terminals Ca(2+) enter through voltage gated calcium channels (CaVs) and bind to a synaptic vesicle (SV) -associated calcium sensor (SV-sensor) to gate fusion and discharge. An open CaV generates a high-concentration plume, or nanodomain of Ca(2+) that dissipates precipitously with distance from the pore. At most fast synapses, such as the frog neuromuscular junction (NMJ), the SV sensors are located sufficiently close to individual CaVs to be gated by single nanodomains. However, at others, such as the mature rodent calyx of Held (calyx of Held), the physiology is more complex with evidence that CaVs that are both close and distant from the SV sensor and it is argued that release is gated primarily by the overlapping Ca(2+) nanodomains from many CaVs. We devised a 'graphic modeling' method to sum Ca(2+) from individual CaVs located at varying distances from the SV-sensor to determine the SV release probability and also the fraction of that probability that can be attributed to single domain gating. This method was applied first to simplified, low and high CaV density model release sites and then to published data on the contrasting frog NMJ and the rodent calyx of Held native synapses. We report 3 main predictions: the SV-sensor is positioned very close to the point at which the SV fuses with the membrane; single domain-release gating predominates even at synapses where the SV abuts a large cluster of CaVs, and even relatively remote CaVs can contribute significantly to single domain-based gating.

摘要

在快速传递的突触前终末,钙离子(Ca²⁺)通过电压门控钙通道(CaV)进入,并与突触小泡(SV)相关的钙传感器(SV传感器)结合,以控制融合和释放。开放的CaV会产生一个高浓度的羽流,即Ca²⁺的纳米域,它会随着与孔的距离急剧消散。在大多数快速突触中,如青蛙神经肌肉接头(NMJ),SV传感器的位置足够靠近单个CaV,以被单个纳米域控制。然而,在其他突触中,如成熟啮齿动物的Held壶腹(Held壶腹),生理学情况更为复杂,有证据表明CaV与SV传感器既有近距离的,也有远距离的,并且有人认为释放主要由许多CaV重叠的Ca²⁺纳米域控制。我们设计了一种“图形建模”方法,以汇总来自位于距SV传感器不同距离处的单个CaV的Ca²⁺,从而确定SV释放概率以及该概率中可归因于单域门控的部分。该方法首先应用于简化的、低CaV密度和高CaV密度的模型释放位点,然后应用于已发表的关于对比青蛙NMJ和啮齿动物Held壶腹天然突触的数据。我们报告了3个主要预测结果:SV传感器的位置非常接近SV与膜融合的点;即使在SV邻接大量CaV簇的突触中,单域释放门控也占主导地位,并且即使相对较远的CaV也可对基于单域的门控做出显著贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58c4/4826128/bd6266c11fae/kchl-09-05-1098793-g001.jpg

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