ATP regulates calcium leak from agonist-sensitive internal calcium stores
ATP regulates calcium leak from agonist-sensitive internal calcium stores
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DOI：
10.1096/fasebj.10.2.8641563
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发表时间：
1996-02-01
期刊：
影响因子：
4.8
通讯作者：
Schulz, I
中科院分区：
文献类型：
--
作者：
Hofer, AM;Curci, S;Schulz, I
在静息条件下，激动剂敏感性Ca库中的稳态[Ca]反映了Ca的主动摄取（通常由SERCA家族的毒胡萝卜素敏感性Ca-ATP酶介导）和被动流出之间的平衡。尽管这种泵-漏循环似乎是钙储存细胞器的共同特性，但对漏途径的性质知之甚少，使用隔室化的mag-fura-2的数字图像处理来检查单个透化的BHK-21成纤维细胞的毒胡萝卜素敏感的内部钙储存中的钙稳态。（低亲和力Ca指示剂），这里显示，Ca从内部储存的泄漏是由细胞溶质ATP浓度特异性调节的，0.375 mM [ATP]中的泄漏速率比4 mM [ATP]中的泄漏速率慢3.6倍在0 Ca/EGTA、毒胡萝卜素、肝素和钌红存在下观察到这些作用，因此似乎不依赖于Ca-ATP酶、InsP（3）受体和ryanodine受体，在多种细胞类型中观察到ATP刺激的渗漏，包括大鼠嗜碱性白血病细胞和小鼠胰腺腺泡细胞。（ADP、GTP、CTP和UTP）和不可水解的ATP类似物（AMP-PNP和ATP gamma S）不能再现ATP的作用，预计细胞代谢的变化和随后的[ATP]改变将通过对被动渗漏途径的影响影响内部钙库的充盈状态，可能导致Ca信号传导和细胞器功能的调节。
Under resting conditions, steady-state [Ca] in agonist-sensitive Ca stores reflects a balance between active uptake (usually mediated by a thapsigargin-sensitive Ca-ATPase of the SERCA family) and passive efflux of Ca. Even though this pump-leak cycle appears to be a common property of Ca-storing organelles, little is known about the nature of the leak pathway, Ca homeostasis in thapsigargin-sensitive internal Ca stores of single permeabilized BHK-21 fibroblasts was examined using digital image processing of compartmentalized mag-fura-2 (a low-affinity Ca indicator), It is shown here that the leak of Ca from internal stores is regulated specifically by the cytosolic ATP concentration, The rate of leak was 3.6 times slower in 0.375 mM [ATP] than in 4 mM [ATP] (Na or Mg salt), These effects were observed in the presence of 0 Ca/EGTA, thapsigargin, heparin, and ruthenium red, and therefore appear to be independent of the Ca-ATPase, the InsP(3) receptor and the ryanodine receptor, The ATP-stimulated leak was seen in a variety of cell types, including rat basophilic leukemia cells and mouse pancreatic acinar cells, Other nucleotides (ADP, GTP, CTP, and UTP) and nonhydrolyzable ATP analogs (AMP-PNP and ATP gamma S) did not reproduce the action of ATP, Changes in cellular metabolism and ensuing alterations in [ATP] will be expected to influence the filling state of internal Ca stores through effects on the passive leak pathway, potentially leading to modulation of Ca signaling and organellar function.