2-aminoethoxydiphenyl borane activates a novel calcium-permeable cation channel
2-aminoethoxydiphenyl borane activates a novel calcium-permeable cation channel
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DOI：
10.1124/mol.63.6.1304
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发表时间：
2003-06-01
影响因子：
3.6
通讯作者：
Putney, JW
中科院分区：
文献类型：
--
作者：
Braun, FJ;Aziz, O;Putney, JW
2-氨基乙氧基二苯基硼烷（2-APB）是一种具有膜渗透性、非竞争性的三磷酸肌醇（IP 3）受体抑制剂，已被广泛用于研究IP 3受体参与钙信号通路。然而，最近在不同细胞类型中的一些研究揭示了2-APB的其他作用位点。在这项研究中，我们研究了2-APB对大鼠嗜碱性白血病（RBL-2 H3 M1）细胞的容量性钙内流和细胞内钙浓度的影响。2-发现APB抑制容量性钙进入，但在浓度大于50 μ M时，观察到2-APB的新效应。当用Gd ~（3+）阻断容量性钙内流时，2-APB引起胞浆Ca ~（2+）增加。这种细胞内Ca 2+的增加不是由细胞质Ca 2+缓冲的改变引起的，也不是由细胞内Ca 2+储存的耗尽引起的或以任何方式受其影响。与细胞内Ca ~（2+）增加有关，在2 mM Ca ~（2+）存在下，2-APB激活质膜上的单通道，其电导接近50 pS。这些通道似乎是非选择性阳离子通道;一价阳离子是电流的主要载体，但对Ca 2+的有限渗透性导致显着的细胞内Ca 2+信号。用切除的贴片进行的实验表明，2-APB从细胞膜的外部激活这些通道。2-APB的这种作用进一步说明了这种化合物的复杂作用，并揭示了RBL-2 H3 m1细胞中存在一种新型的配体门控钙渗透通道。
The membrane-permeable, noncompetitive inositol 1,4,5-trisphosphate (IP3)- receptor inhibitor 2-aminoethoxydiphenyl borane (2-APB) has been widely used to probe for IP3-receptor involvement in calcium signaling pathways. However, a number of recent studies in different cell types revealed other sites of action of 2-APB. In this study, we examined the influence of 2-APB on capacitative calcium entry and intracellular Ca2+ concentrations in rat basophilic leukemia (RBL-2H3 m1) cells. 2-APB was found to inhibit capacitative calcium entry, but at concentrations greater than 50 muM, a new effect of 2-APB was observed. When capacitative calcium entry was blocked with Gd3+, 2-APB caused an increase in cytoplasmic Ca2+. This increase in intracellular Ca2+ was not caused by altered buffering of cytoplasmic Ca2+ and was not caused by or in any way affected by the depletion of intracellular Ca2+ stores. Associated with the increase in intracellular Ca2+, in the presence of 2 mM Ca2+, 2-APB activated single channels in the plasma membrane with a conductance of similar to50 pS. These channels seem to be nonselective cation channels; monovalent cations are the major carriers of current, but finite permeability to Ca2+ leads to a significant intracellular Ca2+ signal. Experiments with excised patches indicate that 2-APB activates these channels from the outer aspect of the cell membrane. This effect of 2-APB further illustrates the complex actions of this compound and reveals the presence in RBL-2H3 m1 cells of a novel, ligand-gated calcium-permeable channel.