Heterogeneity in cytosolic calcium responses to hypoxia in carotid body cells
Heterogeneity in cytosolic calcium responses to hypoxia in carotid body cells
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DOI：
10.1016/0006-8993(95)01122-6
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发表时间：
1996-01-15
期刊：
影响因子：
2.9
通讯作者：
Prabhakar, NR
中科院分区：
文献类型：
--
作者：
Bright, GR;Agani, FH;Prabhakar, NR
以前的研究者报道过，在颈动脉体的单个血管球细胞中，细胞内pH值对缺氧的反应具有异质模式。本研究的目的是研究缺氧是否对球囊细胞的胞质钙（[Ca2+](i)）有类似的影响，如果有，是否在其他细胞类型中也看到了异质反应模式。实验分别取材于成年大鼠颈动脉小体、大鼠嗜铬细胞瘤（PC12）和血管平滑肌（A7r5）细胞。用Fura-2荧光成像测定单个细胞中[Ca2+](i)的变化。用儿茶酚胺荧光法鉴定球囊细胞。[Ca2+](i)在缺氧条件下升高(pO(2) = 35 +/- 8 mmHg；5分钟)，而缺氧诱导的[Ca2+]减少(i)未见。在20%的分离细胞和细胞串中观察到[Ca2+](i)的增加，但聚集的球囊细胞没有反应。反应细胞的钙变化幅度与缺氧刺激成正比。在给定的缺氧挑战下，血管球细胞之间的反应模式有明显的差异。任何给定细胞的反应模式特征都是可复制的。在类似的缺氧水平下，PC12细胞也以[Ca2+](i)的增加做出反应，其反应模式与血管球细胞相似。相比之下，A7r5细胞中[Ca2+](i)的增加只有在持续缺氧（类似于20分钟）时才能看到，并且反应模式的异质性不大。这些结果表明：(a)缺氧使球囊细胞的胞质钙增加；(b)单个细胞的反应模式不同；(c)缺氧诱导的[Ca2+]变化的模式(i)是细胞特异性的。这些结果表明，缺氧诱导的[Ca2+](i)的增加在分泌细胞中比在非分泌细胞中更快。
Previous investigators have reported that intracellular pH responds to hypoxia with a heterogenous pattern in individual glomus cells of the carotid body. The aim of the present study was to examine whether hypoxia had similar effects on cytosolic calcium ([Ca2+](i)) in glomus cells, and if so, whether a heterogenous response pattern is also seen in other cell types. Experiments were performed on glomus cells from adult rat carotid bodies, rat pheochromocytoma (PC12) and vascular smooth muscle (A7r5) cells. Changes in [Ca2+](i) in individual cells were determined by fluorescence imaging using Fura-2. Glomus cells were identified by catecholamine fluorescence. [Ca2+](i) in glomus cells increased in response to hypoxia (pO(2) = 35 +/- 8 mmHg; 5 min), whereas hypoxia induced decreases in [Ca2+](i) were not seen. Increases in [Ca2+](i) were observed in 20% of the isolated cells and strings of cells, but clustered glomus cells never responded. The magnitude of the calcium change in responding cells was proportional to the hypoxic stimulus. Under a given hypoxic challenge, there were marked variations in the response pattern between glomus cells. The response pattern characteristic of any given cell was reproducible. At comparable levels of hypoxia, PC12 cells also responded with an increase in [Ca2+](i) with a heterogenous response pattern similar to that seen in glomus cells. In contrast, increases in [Ca2+](i) in A7r5 cells could be seen only with sustained hypoxia (similar to 20 min), and little heterogeneity in the response patterns was evident. These results demonstrate that: (a) hypoxia increases cytosolic calcium in glomus cells; (b) response patterns were heterogeneous in individual cells; and (c) the pattern of the hypoxia-induced changes in [Ca2+](i) is cell specific. These results suggest that hypoxia-induced increases in [Ca2+](i) are faster in secretory than in non-secretory cells.