Imaging the hierarchical Ca2+ signalling system in HeLa cells
Imaging the hierarchical Ca2+ signalling system in HeLa cells
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DOI：
10.1113/jphysiol.1997.sp021928
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发表时间：
1997-03-01
影响因子：
5.5
通讯作者：
Lipp, P
中科院分区：
文献类型：
--
作者：
Bootman, M;Niggli, E;Lipp, P
1.用共聚焦显微镜观察激素诱导的不可兴奋细胞系(HeLa细胞)内质网(ER)亚细胞钙释放信号。组胺引起两种基本的钙信号：(1)来自单个内质网钙释放通道的钙信号(幅度，30 nM；横向扩展，1.3微米)；(2)由多个钙信号(幅度，170 nM，扩展，4微米)协同激活而产生的钙泡。HeLa细胞中的Ca~(2+)波来自不同数量的起始点，但对于单个细胞，起始点的数目和亚细胞位置是恒定的。全球钙信号的动力学和幅度与所招募的起始点数量成正比。细胞内钙释放反馈的减少引起盐性钙波，揭示了波传播的两个主要步骤：扩散和再生。阈值刺激可诱发流产的钙波，这是由于钙离子的有限募集引起的。从基础水平(BLIP)到中间水平(PUFF)再到钙波，钙信号事件的层次结构是不可兴奋细胞钙信号转导的原型，也类似于心肌细胞中的钙夸克、钙火花和钙波。
1. Confocal microscopy was used to investigate hormone-induced subcellular Ca2+ release signals from the endoplasmic reticulum (ER) in a prototype non-excitable cell line (HeLa cells).2. Histamine application evoked two types of elementary Ca2+ signals: (i) Ca2+ blips arising from single ER Ca2+ release channels (amplitude, 30 nM; lateral spreading, 1.3 mu m); (ii) Ca2+ puffs resulting from the concerted activation of several Ca2+ blips (amplitude, 170 nM; spreading, 4 mu m).3. Ca2+ waves in the HeLa cells arose from a variable number of initiation sites, but for individual cells, the number and subcellular location of the initiation sites were constant. The kinetics and amplitude of global Ca2+ signals were directly proportional to the number of initiation sites recruited.4. Reduction of the feedback inherent in intracellular Ca2+ release caused saltatoric Ca2+ waves, revealing the two principal steps underlying wave propagation: diffusion and regeneration. Threshold stimulation evoked abortive Ca2+ waves, caused by the limited recruitment of Ca2+ puffs.5. The hierarchy of Ca2+ signalling events, from fundamental levels (blips) to intermediate levels (puffs) to Ca2+ waves, is a prototype for Ca2+ signal transduction for non-excitable cells, and is also analogous to the Ca2+ quarks, Ca2+ sparks and Ca2+ waves in cardiac muscle cells.