钙池操纵的Ca^(2+)通道的激活机制研究进展

Advances in understanding the activation mechanism of storeoperated Ca^(2+) channels

钙池操纵的Ca^(2+)通道(store-operated Ca^(2+) channels,SOC)是非兴奋细胞Ca^(2+)内流的主要通道之一,参与多种病理和生理过程,在钙信号通路的研究中,SOC的激活机制一直是人们关注的焦点之一,迄今为止,钙内流因子模型(Ca^(2+) innux factor model,CIF model)和构象耦联模型fconformational coupling model)受到广泛关注.部分学者已经从很多不同类型的细胞中提取出CIF,并证实钙非依赖性的磷脂酶A_2(Ca^(2+)-independent phospholipase A_2,iPLA_2)作为CIF的底物,在某些类型细胞的SOC激活过程中发挥重要作用,并进一步提出了ER- CIF-iPLA_2-CaM-LysoPLs-SOC通路模型.瞬时受体电位(transient receptor potential,TRP)通道蛋白与1.4,5-磷酸肌醇受体(inositol 1,4,5 trisphosphate receptor,IP_3R)的结构连接作为构象耦联模型的基础已被广泛证实,随着对IP_3R,Ryanodine受体、肌动蛋白等在钙信号通路中所发挥作用的深入研究,构象耦联模型将得到不断补充和完善.SOC激活机制的破解,将对进一步完善非兴奋细胞的钙通道特性及其调节机制理论带来重大突破.

As one of the major Ca^2＋ channels for Ca^2＋ influx in non-excitable cells, the store-operated Ca^2＋ channel （SOC） is involved in a variety of pathological and physiological processes. The SOC has received much scientific attention regarding sub-types of the receptor-activated Ca^2＋ channel. The activation mechanisms of SOCs have always been an important focus of research on Ca^2＋signal pathways. However, a generally accepted theory has yet to be established. The Ca^2＋ influx factor （CIF） model and the conformational coupling model are two widely researched models. CIF has been extracted from various types of cells, and it has been proven that Ca^2＋-independentphospholipase A2 is a substrate of CIF, playing a crucial role in activating the SOC in certain cells. These findings led to the ER-CIF-iPLA2- CaM-LysoPLs-SOC pathway model hypothesis. The structural junction between the TRP channel protein and the inositol-1, 4, 5-trisphosphate receptor is the foundation of the conformational coupling model, and has wide acceptance. Future research into the roles of the inositol-1, 4, 5-trisphosphate receptor, the ryanodine receptor and actin in the Ca^2＋ signal pathway should reinforce the conformational coupling model. Deciphering the mechanism of SOC activation will represent a breakthrough in our understanding of the characteristics of this Ca^2＋ channel and its regulative mechanism.