Timing of Dense-Core Vesicle Exocytosis Depends on the Facilitation L-Type Ca Channel in Adrenal Chromaffin Cells

Timing of Dense-Core Vesicle Exocytosis Depends on the Facilitation L-Type Ca Channel in Adrenal Chromaffin Cells
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DOI:
10.1523/jneurosci.18-16-06230.1998
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发表时间:
1998-08
期刊:
The Journal of Neuroscience
影响因子:
--
通讯作者:
A. Elhamdani;Zhuan Zhou;C. R. Artalejo
A. Elhamdani;Zhuan Zhou;C. R. Artalejo
中科院分区:
其他
文献类型:
--
作者:
A. Elhamdani;Zhuan Zhou;C. R. Artalejo

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从致密核心囊泡的分泌据说是慢得多,从典型的突触囊泡,可能是因为非共定位的钙通道和释放网站。我们重新调查了这个问题,通过测量的动力学,从小牛和成年牛的嗜铬细胞中释放的儿茶酚胺。由动作电位刺激的小牛嗜铬细胞的电流记录表现出两个依赖于刺激频率和钙离子进入途径的分泌laviment。短潜伏期反应(25毫秒延迟;“弱耦合”)在较高的频率(7 Hz)更明显,并大大减少毒素,阻断N-和P-型钙通道。钙电流记录显示,成年牛嗜铬细胞缺乏促进通道,几乎所有的分泌弱耦合在这些细胞。强耦合信号的平均延迟在动作电位峰值(在24 ° C下)之后为0.33毫秒,表明致密核心囊泡可以表现出接近神经元中发生的胞吐速率。虽然其他的解释是可能的,这些结果是一致的想法,即促进钙通道共定位与释放网站在小牛嗜铬细胞。基于纳入这一假设的模型的计算表明,这些通道必须在13 nm的分泌位点,以考虑这种快速胞吐。
Secretion from dense-core vesicles is reputedly much slower than that from typical synaptic vesicles, possibly because of noncolocalization of Ca channels and release sites. We reinvestigated this question by measuring the kinetics of catecholamine release in chromaffin cells from calf and adult bovines. Amperometric recording from calf chromaffin cells stimulated by action potentials exhibited two latencies of secretion that depended on both the frequency of stimulation and the pathway of Ca entry. Short-latency responses (25 msec delay; “weakly coupled”) were more apparent at higher frequencies (7 Hz) and were substantially reduced by toxins that blocked N- and P-type Ca channels. Ca current recordings revealed that adult bovine chromaffin cells lack facilitation channels; virtually all secretion was weakly coupled in these cells. The mean delay of the strongly coupled signal was ∼3 msec after the peak of the action potential (at 24°C), indicating that dense-core vesicles can exhibit a rate of exocytosis approaching that occurring in neurons. Although other explanations are possible, these results are consistent with the idea that facilitation Ca channels are colocalized with release sites in calf chromaffin cells. Calculations based on a model incorporating this assumption suggest that these channels must be within 13 nm of secretory sites to account for such rapid exocytosis.