Theoretical Model of Neurotransmitter Release during In Vivo Vesicular Exocytosis Based on a Grainy Biphasic Nano-Structuration of Chromogranins within Dense Core Matrixes

Theoretical Model of Neurotransmitter Release during In Vivo Vesicular Exocytosis Based on a Grainy Biphasic Nano-Structuration of Chromogranins within Dense Core Matrixes
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基于致密核心基质内嗜铬粒蛋白的粒状双相纳米结构的体内囊泡胞吐作用过程中神经递质释放的理论模型

DOI:
10.1149/2.0031604jes
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发表时间:
2016-01-01
影响因子:
3.9
通讯作者:
Amatore, Christian
Amatore, Christian
中科院分区:
工程技术4区
文献类型:
--
作者:
Oleinick, Alexander;Hu, Ren;Amatore, Christian

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致密核心囊泡的胞吐作用是许多细胞释放神经递质的一个重要的普遍过程。这激发了监测和理解囊泡释放事件的强大努力,以推断其生物学和物理化学机制。尽管到目前为止已经取得了很大的成就,但许多实验观察仍然没有得到解释,甚至令人费解,主要是因为他们设想囊泡基质由囊泡膜包裹的均质聚电解质凝聚相组成。这项工作揭示了一种新的致密核心基质模型,该模型基于聚电解质的物理学,涉及由大体积单体和小分子(这里是儿茶酚胺和钙离子)的混合物凝聚的阴离子部分(这里是嗜铬颗粒)的长链。由此得出的结论是,基质不可能是均匀的,但必须由紧密致密的纳米颗粒的分散体组成,这些纳米颗粒浸泡在较不浓缩的相中,涉及松散折叠的嗜铬粒素链,儿茶酚胺阳离子可能在其中以显著的速度扩散。即使这种石榴状的描述在直接的实验测试手段可用之前必须保持本质上的理论,它也导致了一整套预测,这些预测与所有基于对囊泡胞吐的安培监测的实验观察完全一致,包括最近一些极其令人费解的实验观察。(C)提交人(S)2015年。由ECS出版。本文是根据知识共享署名非商业性非衍生品4.0许可证(CC BY-NC-ND,http://creativecommons.org/licenses/by-nc-nd/4.0/),)的条款分发的开放获取文章,该许可证允许在任何介质中非商业性地重复使用、分发和复制,前提是原始作品未以任何方式更改并被正确引用。要获得商业再利用的许可,请发送电子邮件至:OA@Electric Chem.org。[DOI:10.1149/2.0031604 jes]版权所有。
Exocytosis from dense core vesicles is an important ubiquitous process by which neurotransmitters are released frommany cells. This has stimulated strong efforts to monitor and understand vesicular release events in order to infer their biological and physicochemical mechanisms. Though much has been achieved so far, many experimental observations remain unexplained, even puzzling, essentially because they envision that the vesicle matrixes consist of a homogeneous polyelectrolytic condensed phase encapsulated by the vesicles membranes. This work discloses a new model of dense core matrixes based on the physics of polyelectrolytes involving long chains of anionic moieties (here, chromogranins) condensed by a mixture of bulky monocations and small dications (here, catecholamines and calcium ions). It follows that matrixes cannot be homogeneous but necessarily consist of a dispersion of tightly compacted nano-grains immersed in a less condensed phase involving loosely folded chromogranin strands in which catecholamine cations may diffuse at significant rates. Even if such pomegranate-like description has to remain essentially theoretical up to when direct experimental means of testing is available, it leads to a whole set of predictions that are fully coherent with all experimental observations based on amperometric monitoring of vesicular exocytosis including some recent extremely puzzling ones. (C) The Author(s) 2015. Published by ECS. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives 4.0 License (CC BY-NC-ND, http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is not changed in any way and is properly cited. For permission for commercial reuse, please email: oa@electrochem.org. [DOI: 10.1149/2.0031604jes] All rights reserved.