A study on the molecular hasis of intracellular Ca^<2+> stores

细胞信号传导需要通过Ca^<2+>释放通道有效地从细胞内储存的Ca^<2+>动员，以及预测离子在肌浆/内质网（SR/ER）膜上的反向运动，以平衡Ca^<2+>释放^<1-7>所产生的瞬态负电位。Ca^<2+>释放通道在15年前就被克隆出来了^<8,9>，而推测的反离子通道的分子特性仍然未知。在这里，我们报告了两种TRIC（三聚体细胞内阳离子）通道亚型，它们在动物细胞类型的细胞内储存中差异表达。TRIC亚型包含三个建议的跨膜片段，形成具有子弹样结构的同源三聚体。电生理测量纯化TRIC制剂鉴定单价阳离子选择通道。在trc基因敲除的胚胎心力衰竭小鼠中，突变心肌细胞在细胞内处理Ca^<2+>时表现出严重的功能障碍。trio缺乏的骨骼肌SR表现为K+通透性降低，以及Ca^<2+>火花信号和电压诱导的Ca^<2+>释放改变。因此，TRIC通道与长期寻找的与SR/ER Ca^<2+>释放同步的反离子通道密切对应。

Cell signaling requires efficient Ca^<2+> mobilization from intracellular stores through Ca^<2+> release channels, as well as predicted counter movement of ions across the sarcoplasmic/endoplasmic reticulum (SR/ER) membrane to balance the transient negative potential generated by Ca^<2+> release^<1-7>. Ca^<2+> release channels were cloned more than 15 years ago^<8,9>, whereas molecular identity of putative counterion channels remains unknown. Here we report two TRIC (trimeric intracellular cation) channel subtypes that are differentially expressed on intracellular stores in animal cell types. TRIC subtypes contain three proposed transmembrane segments and form homo-trimers with a bullet-like structure. Electrophysiological measurements with purified TRIC preparations identify a monovalent cation-selective channel. In TRIC-knockout mice suffering embryonic cardiac failure, mutant cardiac myocytes display severe dysfunction in intracellular Ca^<2+> handling. The TRIO-deficient skeletal muscle SR shows reduced K+ permeability, as well as altered Ca^<2+> spark signaling and voltage-induced Ca^<2+> release. Therefore, TRIC channels correspond closely to the long-sought counter-ion channels that function in synchronization with SR/ER Ca^<2+> release.