DEPLETION OF INTRACELLULAR CALCIUM STORES ACTIVATES A CALCIUM CURRENT IN MAST-CELLS
DEPLETION OF INTRACELLULAR CALCIUM STORES ACTIVATES A CALCIUM CURRENT IN MAST-CELLS
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DOI：
10.1038/355353a0
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发表时间：
1992-01-23
期刊：
影响因子：
64.8
通讯作者：
PENNER, R
中科院分区：
文献类型：
--
作者：
HOTH, M;PENNER, R
在许多细胞类型中，受体介导的Ca 2+从内部储存释放之后是Ca 2+跨质膜流入1-3。Ca 2+的持续进入被认为部分是由于细胞内Ca 2+池的耗尽4，5。大多数研究通过测量Ca 2+激活电流6-9或使用Mn 2+猝灭的Fura-2间接表征了Ca 2+内流，Mn 2+在一些细胞中通过相同的内流途径进入细胞10，11，但只有少数研究更直接地研究了这种Ca 2+进入途径12-14。我们结合膜片钳和Fura-2测量，以监测膜电流在肥大细胞的条件下，细胞内的Ca 2+存储被清空的肌醇1，4，5-三磷酸，离子霉素，或过量的Ca 2+螯合剂EGTA。通过这些独立的机制消耗Ca 2+池通常诱导持续的钙内向电流的激活，该电流对Ca 2+离子的选择性高于Ba 2+、Sr 2+和Mn 2+。这种钙电流，我们称之为I（CRAC）（钙释放激活钙），不是电压激活的，并显示出特征性的内向整流。这可能是电不可兴奋细胞在受体刺激后维持升高的细胞内Ca 2+浓度并补充其空Ca 2+库的机制。
IN many cell types, receptor-mediated Ca2+ release from internal stores is followed by Ca2+ influx across the plasma membrane 1-3. The sustained entry of Ca2+ is thought to result partly from the depletion of intracellular Ca2+ pools 4,5. Most investigations have characterized Ca2+ influx indirectly by measuring Ca2+-activated currents 6-9 or using Fura-2 quenching by Mn2+, which in some cells enters the cells by the same influx pathway 10,11 But only a few studies have investigated this Ca2+ entry pathway more directly 12-14. We have combined patch-clamp and Fura-2 measurements to monitor membrane currents in mast cells under conditions where intracellular Ca2+ stores were emptied by either inositol 1,4,5-trisphosphate, ionomycin, or excess of the Ca2+ chelator EGTA. The depletion of Ca2+ pools by these independent mechanisms commonly induced activation of a sustained calcium inward current that was highly selective for Ca2+ ions over Ba2+, Sr2+ and Mn2+. This Ca2+ current, which we term I(CRAC) (calcium release-activated calcium), is not voltage-activated and shows a characteristic inward rectification. It may be the mechanism by which electrically nonexcitable cells maintain raised intracellular Ca2+ concentrations and replenish their empty Ca2+ stores after receptor stimulation.