STORE-OPERATED Ca2+ CHANNELS AND MICRODOMAINS OF Ca2+ IN LIVER CELLS
STORE-OPERATED Ca2+ CHANNELS AND MICRODOMAINS OF Ca2+ IN LIVER CELLS
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DOI：
10.1111/j.1440-1681.2008.05095.x
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发表时间：
2009-01-01
影响因子：
2.9
通讯作者：
Rychkov, Grigori Y.
中科院分区：
文献类型：
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作者：
Barritt, Greg J.;Litjens, Tom L.;Rychkov, Grigori Y.
胞质Ca 2+浓度（[Ca 2 +]（cyt））的振荡性增加在肝细胞的激素调节中起重要作用。[Ca 2 +]（cyt）的增加需要Ca 2+从内质网（ER）释放并穿过质膜进入。细胞池操纵的Ca 2+通道（SOC）由ER腔中Ca 2+的减少激活，负责维持足够的ER Ca 2+。采用膜片钳记录和荧光Ca ~（2+）报告基因Fura-2的实验表明，大鼠肝细胞中只有一种SOC。尽管CRAC通道孔蛋白Orai 1和CRAC通道Ca 2+传感器基质相互作用分子1（stromal interaction molecule 1，STIM 1）是肝细胞SOC的组成部分，但SOC的激活机制，特别是ER亚区的作用，最近的实验已经使用了瞬时受体电位香草素1（TRPV 1）非选择性阳离子通道，异位表达于肝细胞中，和胆汁酸来消耗来自不同ER亚区的Ca 2+。这些研究的结果提供了证据表明，只有一小部分的ER是需要STIM 1重新分配和激活SOCS.It的结论是，不同的钙离子在ER和胞质空间的微域是重要的SOCs的激活和钙离子在肝细胞中的信号作用。未来的实验将进一步研究这些微区的性质。
Oscillatory increases in the cytoplasmic Ca2+ concentration ([Ca2+](cyt)) play essential roles in the hormonal regulation of liver cells. Increases in [Ca2+](cyt) require Ca2+ release from the endoplasmic reticulum (ER) and Ca2+ entry across the plasma membrane.Store-operated Ca2+ channels (SOCs), activated by a decrease in Ca2+ in the ER lumen, are responsible for maintaining adequate ER Ca2+. Experiments using patch-clamp recording and the fluorescent Ca2+ reporter fura-2 indicate there is only one type of SOC in rat liver cells. These SOCs have a high selectivity for Ca2+ and properties essentially indistinguishable from those of Ca2+ release-activated Ca2+ (CRAC) channels.Although Orai1, a CRAC channel pore protein, and stromal interaction molecule 1 (STIM1), a CRAC channel Ca2+ sensor, are components of liver cell SOCs, the mechanism of activation of SOCs, and in particular the role of subregions of the ER, are not well understood.Recent experiments have used the transient receptor potential vanilloid 1 (TRPV1) non-selective cation channel, ectopically expressed in liver cells, and a choleretic bile acid to deplete Ca2+ from different ER subregions. The results of these studies have provided evidence that only a small component of the ER is required for STIM1 redistribution and the activation of SOCs.It is concluded that different Ca2+ microdomains in the ER and cytoplasmic space are important in both the activation of SOCs and in the signalling actions of Ca2+ in liver cells. Future experiments will investigate the nature of these microdomains further.