Store-operated calcium entry is present in HL-1 cardiomyocytes and contributes to resting calcium.
Store-operated calcium entry is present in HL-1 cardiomyocytes and contributes to resting calcium.
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DOI：
10.1016/j.bbrc.2011.10.133
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发表时间：
2011-12-09
影响因子：
3.1
通讯作者：
Wacker, Michael J.
中科院分区：
文献类型：
--
作者：
Touchberry, Chad D.;Elmore, Chris J.;Nguyen, Tien M.;Andresen, Jon J.;Zhao, Xiaoli;Orange, Matthew;Weisleder, Noah;Brotto, Marco;Claycomb, William C.;Wacker, Michael J.
钙池操纵性钙内流（SOCE）在心脏中具有重要的生理和病理意义，特别是在心脏肥大期间。然而，测量在SOCE过程中细胞内Ca 2+的变化是非常困难的成年原代心肌细胞的研究。因此，需要一种稳定可靠的体外SOCE模型，用于检测心脏药物和研究SOCE在心脏病理学中的作用。HL-1细胞是唯一的永生心肌细胞系，可持续分裂和自发收缩，同时保持成人心肌细胞的表型特征。到目前为止，尚未在HL-1心肌细胞系中研究SOCE的作用。我们首次报告，这些细胞表达基质相互作用分子1（STIM 1）和钙释放激活的钙离子（CRAC）通道Orai 1，这是SOCE机制的重要组成部分。此外，在HL-1细胞中，SOCE与肌浆网（SR）-Ca 2+释放紧密偶联，并且在电压依赖性Ca 2+通道（L型和T型通道）或反向模式Na+/Ca 2+交换器（NCX）抑制剂存在下，这种反应不受损害。我们能够用已知的SOCE抑制剂（BTP-2和SKF-96365）和用RNAi靶向敲低Orai 1来消除SOCE应答。此外，Orai 1的敲低导致较低的基线Ca 2+和对毒胡萝卜素（TG）和咖啡因的减弱反应，表明SOCE可能在心肌细胞非应激条件下的Ca 2+稳态中发挥作用。目前，对心肌细胞中的SOCE了解甚少，本研究结果表明，HL-1细胞将在研究SOCE在心脏中的作用方面发挥重要作用。
Store-operated Ca2+ entry (SOCE) has recently been shown to be of physiological and pathological importance in the heart, particularly during cardiac hypertrophy. However, measuring changes in intracellular Ca2+ during SOCE is very difficult to study in adult primary cardiomyocytes. As a result there is a need for a stable and reliable in vitro model of SOCE which can be used to test cardiac drugs and investigate the role of SOCE in cardiac pathology. HL-1 cells are the only immortal cardiomyocyte cell line available that continuously divides and spontaneously contracts while maintaining phenotypic characteristics of the adult cardiomyocyte. To date the role of SOCE has not yet been investigated in the HL-1 cardiac cell line. We report for the first time that these cells express stromal interaction molecule 1 (STIM1) and the Ca2+ release-activated Ca2+ (CRAC) channel Orai1, which are essential components of the SOCE machinery. In addition, SOCE is tightly coupled to sarcoplasmic reticulum (SR)-Ca2+ release in HL-1 cells, and such response was not impaired in the presence of voltage dependent Ca2+ channels (L-type and T-type channels) or reverse mode Na+/ Ca2+ exchanger (NCX) inhibitors. We were able to abolish the SOCE response with known SOCE inhibitors (BTP-2 and SKF-96365) and by targeted knockdown of Orai1 with RNAi. In addition, knockdown of Orai1 resulted in lower baseline Ca2+ and an attenuated response to thapsigargin (TG) and caffeine, indicating that SOCE may play a role in Ca2+ homeostasis during unstressed conditions in cardiomyocytes. Currently, there is little knowledge about SOCE in cardiomyocytes, and the present results suggest that HL-1 cells will be of great utility in investigating the role of SOCE in the heart.
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衰老骨骼肌中钙池操纵的 Ca2+ 进入受损。
影响因子：
7.8
作者：
Zhao, Xiaoli;Weisleder, Noah;Thornton, Angela;Oppong, Yaa;Campbell, Rachel;Ma, Jianjie;Brotto, Marco
通讯作者：
Brotto, Marco
影响因子：
4
作者：
Malli R;Naghdi S;Romanin C;Graier WF
通讯作者：
Graier WF
影响因子：
4.8
作者：
Chandrasekar, B;Mummidi, S;Nemer, M
通讯作者：
Nemer, M
影响因子：
37.8
作者：
Hulot JS;Fauconnier J;Ramanujam D;Chaanine A;Aubart F;Sassi Y;Merkle S;Cazorla O;Ouillé A;Dupuis M;Hadri L;Jeong D;Mühlstedt S;Schmitt J;Braun A;Bénard L;Saliba Y;Laggerbauer B;Nieswandt B;Lacampagne A;Hajjar RJ;Lompré AM;Engelhardt S
通讯作者：
Engelhardt S
影响因子：
21.3
作者：
Peinelt, Christine;Vig, Monika;Kinet, Jean-Pierre
通讯作者：
Kinet, Jean-Pierre