Stimulus-secretion coupling in neurohypophysial nerve endings: a role for intravesicular sodium?

Stimulus-secretion coupling in neurohypophysial nerve endings: a role for intravesicular sodium?
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神经垂体神经末梢的刺激-分泌耦合:膀胱内钠的作用?

DOI:
10.1073/pnas.96.6.3206
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发表时间:
1999
影响因子:
11.1
通讯作者:
Nicaise,G
Nicaise,G
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Thirion,S;Troadec,JD;Pivovarova,NB;Pagnotta,S;Andrews,SB;Leapman,RD;Nicaise,G

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人们普遍认为 Ca 本质上参与调节分泌,但这种阳离子以及 Na 等其他阳离子的作用尚不清楚。一个说明性的例子发生在神经垂体分泌中,其中实验诱导的Na + 胞质浓度的增加可以诱导连续的神经肽释放。相反,胞质 Ca2+ 的增加仅具有短暂的刺激作用。 Ca2+ 的促分泌靶点尚不清楚;正如通常假设的那样,它们可能是细胞质的,但它们也可能是囊泡内的,特别是考虑到富含钙的分泌囊泡优先分泌的证据。在目前的工作中,我们研究了这些阳离子在刺激-分泌耦合过程中进出分泌囊泡的运动。用钾(55 mM)去极化刺激离体大鼠神经垂体神经末梢,并在刺激开始后6分钟(分泌峰值)和20分钟,通过定量X射线微量分析测量各个分泌囊泡的元素含量。发现去极化引起的囊内 Na+ 浓度短暂增加与分泌的开始一致。此外,只有预计的一小部分外周囊泡(可能是对接的囊泡)负载有 Na+。富含 Na+ 的囊泡的低硫浓度很可能是由囊泡肿胀引起的。结果表明,通过Na+/Ca2+交换或瞬时融合孔开放而发生的对接囊泡中的高囊泡内Na+浓度是胞吐作用中的近端事件。
It is generally accepted that Ca is essentially involved in regulated secretion, but the role of this cation, as well as others such as Na, is not well understood. An illustrative example occurs in neurohypophysial secretion, where an experimentally induced increase in the cytosolic concentration of Na+can induce continuous neuropeptide release. In contrast, an increase in cytosolic Ca2+will have only a transient stimulatory effect. The secretion-promoting targets for Ca2+are not known; they may be cytosolic, as is usually assumed, but they may also be intravesicular, especially in view of evidence that Ca-rich secretory vesicles are preferentially secreted. In the present work, we have investigated the movements of these cations into and out of secretory vesicles during stimulus–secretion coupling. Isolated rat neurohypophysial nerve endings were stimulated by potassium (55 mM) depolarization, and at 6 min (peak secretion) and 20 min after the onset of stimulation, the elemental content of individual secretory vesicles was measured by quantitative x-ray microanalysis. A depolarization-induced transient increase in intravesicular Na+concentration was found to coincide with the onset of secretion. Moreover, only a predicted small fraction of peripheral vesicles—presumably the docked ones—were Na+-loaded. The low sulfur concentration of Na+-rich vesicles most likely resulted from vesicle swelling. The results suggest that high intravesicular Na+concentrations in docked vesicles, occurring by Na+/Ca2+exchange or by transient fusion pore opening, is a proximal event in exocytosis.
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DOI: 10.1073/pnas.78.10.5958
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