Inositol 1,4,5-trisphosphate-induced Ca2+ release is inhibited by mitochondrial depolarization
Inositol 1,4,5-trisphosphate-induced Ca2+ release is inhibited by mitochondrial depolarization
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DOI：
10.1042/0264-6021:3470593
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发表时间：
2000-04-15
影响因子：
4.1
通讯作者：
Bootman, MD
中科院分区：
文献类型：
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作者：
Collins, TJ;Lipp, P;Bootman, MD
我们研究了去极化线粒体膜电位（Δ psi（mit））对Ca 2+信号产生的后果，通过肌醇1，4，5-三磷酸受体（InsP（3）R）在细胞刺激的HeLa细胞。发现羰基氰对三氟甲氧基苯腙（FCCP）或抗霉素A（+）寡霉素的混合物能迅速地消除Δ psi（mit）。线粒体去极化增强了响应于短暂应用的Ca 2+动员激素的细胞数量，并延长了激素洗脱后胞浆Ca 2+的恢复;与去除被动Ca 2+缓冲液的效果一致。然而，随着重复应用相同的激素浓度的响应细胞的数量和峰值Ca 2+的变化，观察到进行性下降。使用不同的Ca 2+动员激素和膜渗透性Ins（1，4，5）P-3 eater观察到Ca 2+信号传导的抑制。冲洗FCCP后，Ca 2+信号恢复的时间过程类似于Delta psi（mit）的重建。全球测量表明，没有明显的因素，如pH值的变化，ATP浓度，细胞氧化还原状态，渗透性转换孔激活或减少Ca 2 +-存储负载出现的Ca 2+信号的抑制。因此，我们认为这些因素中的一个或多个的局部变化，作为去极化Delta psi（mit）的结果，阻止了InsP（3）R的激活。
We investigated the consequences of depolarizing the mitochondrial membrane potential (Delta psi(mit)) on Ca2+ signals arising via inositol 1,4,5-trisphosphate receptors (InsP(3)R) in hormone-stimulated HeLa cells. Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) or a mixture of antimycin A(+) oligomycin were found to rapidly depolarize Delta psi(mit). Mitochondrial depolarization enhanced the number of cells responding to a brief application of a Ca2+-mobilizing hormone and prolonged the recovery of cytosolic Ca2+ after washout of the hormone; effects consistent with the removal of a passive Ca2+ buffer. However, with repeated application of the same hormone concentration both the number of responsive cells and peak Ca2+ changes were observed to progressively decline. The inhibition of Ca2+ signalling was observed using different Ca2+ mobilizing hormones and also with a membrane-permeant Ins(1,4,5)P-3 eater. Upon washout of FCCP, the Ca2+ signals recovered with a time course similar to the re-establishment of Delta psi(mit). Global measurements indicated that none of the obvious factors such as changes in pH, ATP concentration, cellular redox state, permeability transition pore activation or reduction in Ca2+-store loading appeared to underlie the inhibition of Ca2+ signalling. We therefore suggest that local changes in one or more of these factors, as a consequence of depolarizing Delta psi(mit), prevents InsP(3)R activation.