Functional ryanodine receptors in the membranes of neurohypophysial secretory granules.
Functional ryanodine receptors in the membranes of neurohypophysial secretory granules.
复制标题
DOI：
10.1085/jgp.201311110
复制
发表时间：
2014-06
期刊：
影响因子：
--
通讯作者：
Lemos JR
中科院分区：
文献类型：
--
作者：
McNally JM;Custer EE;Ortiz-Miranda S;Woodbury DJ;Kraner SD;Salzberg BM;Lemos JR
在大的致密核心囊泡中，从ryanodine敏感的储存中局部释放的钙可以调节神经垂体末梢的神经肽分泌。高度本地化的Ca2+释放事件的特点是在几个神经元制剂。在小鼠神经垂体终末（NHTs），这种事件，所谓的Ca 2 + syntillas，似乎从ryanodine敏感的细胞内Ca 2+池发出。细胞内Ca 2+的传统来源似乎在NHT中缺乏。因此，我们已经测试的假设，大致密核心囊泡（LDCV），其中含有大量的钙，代表这些syntillas的来源。在这里，使用荧光免疫标记和免疫金标记的电子显微照片的NHTs，我们表明，2型兰尼碱受体（RyRs）的本地化，特别是LDCV。此外，一个大的电导非特异性阳离子通道，这是以前确定的囊泡膜，并具有类似的RyR的生物物理特性，是一个RyR的特征的方式受到影响：它被激活的RyR激动剂ryanodine（在低浓度）的存在下，并阻止RyR拮抗剂钌红。此外，神经肽释放实验表明，这些相同的RyR激动剂和拮抗剂调节Ca2+引起的神经肽从透化NHT释放。此外，安培记录的自发释放事件从人工发射机加载终端证实了这些ryanodine的影响。总的来说，我们的研究结果表明RyR依赖性合成细胞可以代表囊泡储存中Ca 2+的动员。在胞吐的精确位置处的这种局部囊泡Ca2+释放事件可以提供能够生理地调节神经肽释放的Ca2+放大机制。
Localized calcium release from ryanodine-sensitive stores in large dense core vesicles may modulate secretion of neuropeptides from neurohypophysial terminals. Highly localized Ca2+ release events have been characterized in several neuronal preparations. In mouse neurohypophysial terminals (NHTs), such events, called Ca2+ syntillas, appear to emanate from a ryanodine-sensitive intracellular Ca2+ pool. Traditional sources of intracellular Ca2+ appear to be lacking in NHTs. Thus, we have tested the hypothesis that large dense core vesicles (LDCVs), which contain a substantial amount of calcium, represent the source of these syntillas. Here, using fluorescence immunolabeling and immunogold-labeled electron micrographs of NHTs, we show that type 2 ryanodine receptors (RyRs) are localized specifically to LDCVs. Furthermore, a large conductance nonspecific cation channel, which was identified previously in the vesicle membrane and has biophysical properties similar to that of an RyR, is pharmacologically affected in a manner characteristic of an RyR: it is activated in the presence of the RyR agonist ryanodine (at low concentrations) and blocked by the RyR antagonist ruthenium red. Additionally, neuropeptide release experiments show that these same RyR agonists and antagonists modulate Ca2+-elicited neuropeptide release from permeabilized NHTs. Furthermore, amperometric recording of spontaneous release events from artificial transmitter-loaded terminals corroborated these ryanodine effects. Collectively, our findings suggest that RyR-dependent syntillas could represent mobilization of Ca2+ from vesicular stores. Such localized vesicular Ca2+ release events at the precise location of exocytosis could provide a Ca2+ amplification mechanism capable of modulating neuropeptide release physiologically.
登录
查看更多内容
影响因子：
4.5
作者：
Divangahi M;Balghi H;Danialou G;Comtois AS;Demoule A;Ernest S;Haston C;Robert R;Hanrahan JW;Radzioch D;Petrof BJ
通讯作者：
Petrof BJ
影响因子：
4
作者：
Berridge, Michael J.
通讯作者：
Berridge, Michael J.
影响因子：
3
作者：
Custer, Edward E.;Ortiz-Miranda, Sonia;Lemos, Jose R.
通讯作者：
Lemos, Jose R.
影响因子：
5.3
作者：
Carter, AG;Vogt, KE;Regehr, WG
通讯作者：
Regehr, WG
影响因子：
5.3
作者：
Conti, R;Tan, YP;Llano, I
通讯作者：
Llano, I