Suppression of Ca2+ syntillas increases spontaneous exocytosis in mouse adrenal chromaffin cells.
Suppression of Ca2+ syntillas increases spontaneous exocytosis in mouse adrenal chromaffin cells.
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DOI：
10.1085/jgp.200910285
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发表时间：
2009-10
期刊：
影响因子：
--
通讯作者：
De Crescenzo V
中科院分区：
文献类型：
--
作者：
Lefkowitz JJ;Fogarty KE;Lifshitz LM;Bellve KD;Tuft RA;ZhuGe R;Walsh JV Jr;De Crescenzo V
神经分泌生理学的一个中心概念是，由于Ca2+内流引起质浆Ca2+通道附近的胞浆[Ca2+]升高引起胞外分泌。在这里，我们研究了在ryanodine受体（RYRs）附近的局灶胞浆[Ca2+]的增加对自发胞外分泌的影响，这是由于内部储存以Ca2+ syntilla的形式释放所致。Ca2+ syntilla是由RYRs介导的局灶胞浆瞬变，我们首次在下丘脑大细胞神经元末梢发现。（闪烁，拉丁语为火花；存在于神经末梢，通常是突触结构。）我们还在小鼠肾上腺染色质细胞中观察到Ca2+合成酶。在这里，我们研究Ca2+合成酶对嗜铬细胞胞吐的影响。在这样一项关于诱导胞外分泌的研究中，Ca2+有两种来源：一种是由于细胞外部通过电压门控Ca2+通道流入，另一种是由于细胞内储存的释放。为了消除Ca2+内流引起的并发症，我们检查了未激活内流的自发胞吐。我们在此报告，减少合成酶导致自发胞吐增加，测量电流。两个独立的实验线都得出了这个结论。在一个案例中，雷亚诺定阻止了从商店的释放；在另一项实验中，使用大麻素和咖啡因将部分储存物清空，之后合成物减少。我们得出结论，Ca2+ syntilla行为抑制自发胞吐，我们提出了一个简单的模型来定量解释这种作用的syntilla。
A central concept in the physiology of neurosecretion is that a rise in cytosolic [Ca2+] in the vicinity of plasmalemmal Ca2+ channels due to Ca2+ influx elicits exocytosis. Here, we examine the effect on spontaneous exocytosis of a rise in focal cytosolic [Ca2+] in the vicinity of ryanodine receptors (RYRs) due to release from internal stores in the form of Ca2+ syntillas. Ca2+ syntillas are focal cytosolic transients mediated by RYRs, which we first found in hypothalamic magnocellular neuronal terminals. (scintilla, Latin for spark; found in nerve terminals, normally synaptic structures.) We have also observed Ca2+ syntillas in mouse adrenal chromaffin cells. Here, we examine the effect of Ca2+ syntillas on exocytosis in chromaffin cells. In such a study on elicited exocytosis, there are two sources of Ca2+: one due to influx from the cell exterior through voltage-gated Ca2+ channels, and that due to release from intracellular stores. To eliminate complications arising from Ca2+ influx, we have examined spontaneous exocytosis where influx is not activated. We report here that decreasing syntillas leads to an increase in spontaneous exocytosis measured amperometrically. Two independent lines of experimentation each lead to this conclusion. In one case, release from stores was blocked by ryanodine; in another, stores were partially emptied using thapsigargin plus caffeine, after which syntillas were decreased. We conclude that Ca2+ syntillas act to inhibit spontaneous exocytosis, and we propose a simple model to account quantitatively for this action of syntillas.
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