T-Type voltage-sensitive calcium channels mediate mechanically-induced intracellular calcium oscillations in osteocytes by regulating endoplasmic reticulum calcium dynamics.
T-Type voltage-sensitive calcium channels mediate mechanically-induced intracellular calcium oscillations in osteocytes by regulating endoplasmic reticulum calcium dynamics.
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DOI：
10.1016/j.bone.2016.04.018
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发表时间：
2016-07
期刊：
影响因子：
4.1
通讯作者：
Guo XE
中科院分区：
文献类型：
--
作者：
Brown GN;Leong PL;Guo XE
骨细胞对机械刺激最早的反应之一是细胞内钙离子的升高，尤其是骨细胞在承受负荷时表现出强烈的钙振荡。以前的研究表明内质网(ER)和T型电压敏感钙通道(VSCC)在这些反应中都有作用，但它们的相互作用或相对贡献尚未被研究。本研究通过观察钙离子在胞浆和内质网中的动态变化，探讨ER和T型通道在骨细胞钙信号转导中的作用。我们证明，抑制骨细胞中的T型VSCC显著减少了钙离子细胞色素反应的数量，并影响了钙离子内质网的耗竭动力学。同时观察这些空间之间的钙交换发现，细胞内钙离子的升高和内质网内钙离子的降低之间具有高度的同步性，这种同步性在挑战T型VSCC后显著降低。我们进一步证实，这种作用是通过内质网直接介导的，而不是通过存储操作的钙内流(SOCE)途径。综上所述，我们的数据提示，T型VSCC促进骨细胞内钙离子内质网的恢复，以维持机械诱导的钙振荡，揭示了骨细胞作为力学传感器的行为的新机制。
One of the earliest responses of bone cells to mechanical stimuli is a rise in intracellular calcium (Ca2+), and osteocytes in particular exhibit robust oscillations in Ca2+ when subjected to loading. Previous studies implicate roles for both the endoplasmic reticulum (ER) and T-Type voltage-sensitive calcium channels (VSCC) in these responses, but their interactions or relative contributions have not been studied. By observing Ca2+ dynamics in the cytosol (Ca2+cyt) and the ER (Ca2+ER), the focus of this study was to explore the role of the ER and T-Type channels in Ca2+ signaling in bone cells. We demonstrate that inhibition of T-Type VSCC in osteocytes significantly reduces the number of Ca2+cyt responses and affects Ca2+ER depletion dynamics. Simultaneous observation of Ca2+ exchange among these spaces revealed high synchrony between rises in Ca2+cyt and depressions in Ca2+ER, and this synchrony was significantly reduced by challenging T-Type VSCC. We further confirmed that this effect was mediated directly through the ER and not through store-operated Ca2+ entry (SOCE) pathways. Taken together, our data suggests that T-Type VSCC facilitate the recovery of Ca2+ER in osteocytes to sustain mechanically-induced Ca2+ oscillations, uncovering a new mechanism underlying the behavior of osteocytes as mechanosensors.