Subcellular Ca2+ signals underlying waves and graded responses in HeLa cells
Subcellular Ca2+ signals underlying waves and graded responses in HeLa cells
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DOI：
10.1016/s0960-9822(02)00609-7
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发表时间：
1996-07-01
期刊：
影响因子：
9.2
通讯作者：
Berridge, MJ
中科院分区：
文献类型：
--
作者：
Bootman, MD;Berridge, MJ
背景资料：许多激动剂诱发的细胞内Ca 2+信号具有复杂的时空排列，并且被观察为重复的Ca 2+尖峰和Ca 2+波。揭示这些复杂信号是如何产生的关键在于理解细胞内Ca 2+池的功能结构。以前的成像研究，使用相对较大的细胞，如卵母细胞和肌细胞，已经确定了亚细胞基本Ca 2+信号，表明细胞内Ca 2+池从功能上离散的位点释放Ca 2+。然而，目前尚不清楚较小细胞中的细胞内Ca 2+池是否具有类似的结构，以及这些亚细胞信号如何促成全局尖峰和波。我们在单个Fura 2负载的HeLa细胞对组胺的反应中检测到亚细胞Ca ~（2+）信号，其中一些信号的时空特性与在其他细胞中观察到的基本Ca ~（2+）信号相似，亚细胞Ca 2+信号在再生Ca 2+波之前的“起搏器”Ca 2+上升期间特别明显。在这种起搏过程中，最初在Ca ~（2+）波起源的区域观察到Ca ~（2+）信号，但在产生Ca ~（2+）波之前，Ca ~（2+）信号变得更加广泛和频繁。在波后Ca ~（2+）增加期间，以及在阈值组胺浓度诱发的低幅度Ca ~（2+）反应期间，观察到类似的局部信号。HeLa细胞内钙池是由许多功能离散的单位组成的。在刺激时，这些单位产生局部的Ca 2+信号。这些单位的顺序激活和求和导致Ca 2+波传播，此外，这些单位的差异募集可能是细胞内Ca 2+信号的分级幅度的基础。
Background: Many agonist-evoked intracellular Ca2+ signals have a complex spatio-temporal arrangement, and are observed as repetitive Ca2+ spikes and Ca2+ waves. The key to revealing how these complex signals are generated lies in understanding the functional structure of the intracellular Ca2+ pool, Previous imaging studies, using relatively large cells such as oocytes and myocytes, have identified subcellular elementary Ca2+ signals, indicating that the intracellular Ca2+ pool releases Ca2+ from functionally discrete sites. However, it is unclear whether the intracellular Ca2+ pool in smaller cells has a similar architecture, and how such subcellular signals would contribute to global spikes and waves.Results: We detected subcellular Ca2+ signals during the response of single Fura2-loaded HeLa cells to histamine, The spatio-temporal properties of some of these signals were similar to the elementary Ca2+ signals observed in other cells, Subcellular Ca2+ signals were particularly obvious during the 'pacemaker' Ca2+ rise that preceded the regenerative Ca2+ wave. During this pacemaker, the Ca2+ signals were observed initially in the region from which the Ca2+ wave originated, but became more widespread and frequent until a Ca2+ wave was spawned, Similar localized signals were seen during the post-wave Ca2+ increase, and during the low-amplitude Ca2+ responses evoked by threshold histamine concentrations.Conclusions: The intracellular Ca2+ pool in HeLa cells is composed of many functionally discrete units. Upon stimulation, these units produce localized Ca2+ signals. The sequential activation and summation of these units results in Ca2+ wave propagation and, furthermore, the differential recruitment of these units may underlie the graded amplitude of the intracellular Ca2+ signals.