Sensing intracellular calcium ions using a manganese-based MRI contrast agent
Sensing intracellular calcium ions using a manganese-based MRI contrast agent
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DOI：
10.1038/s41467-019-08558-7
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发表时间：
2019-02-22
影响因子：
16.6
通讯作者：
Jasanoff, Alan
中科院分区：
文献类型：
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作者：
Barandov, Ali;Badelle, Benjamin B.;Jasanoff, Alan
钙离子在几乎所有细胞的信号转导中都是必不可少的，在这些细胞中，它们协调从胚胎发育到神经功能的各种过程。尽管用于细胞内钙成像的光学探针已经存在几十年了，但开发用于非侵入性检测深层组织和完整生物中的细胞内钙信号的探针仍然是一个挑战。为了解决这个问题，我们合成了一种基于锰的顺磁造影剂ManICS1-AM，旨在渗透细胞，经酯酶裂解，并允许通过磁共振成像(MRI)监测细胞内钙水平。当药物或光遗传工具刺激加载ManICS1-AM的细胞时，MRI对比度会发生变化；反应直接与使用荧光钙指示剂获得的信号平行。此外，将ManICS1-AM引入啮齿动物大脑，可以基于MRI测量光学无法接触到的大脑区域的神经激活。因此，这些结果验证了ManICS1-AM是一种与MRI提供的广泛穿透深度和视野兼容的钙传感器。
Calcium ions are essential to signal transduction in virtually all cells, where they coordinate processes ranging from embryogenesis to neural function. Although optical probes for intracellular calcium imaging have been available for decades, the development of probes for noninvasive detection of intracellular calcium signaling in deep tissue and intact organisms remains a challenge. To address this problem, we synthesized a manganese-based paramagnetic contrast agent, ManICS1-AM, designed to permeate cells, undergo esterase cleavage, and allow intracellular calcium levels to be monitored by magnetic resonance imaging (MRI). Cells loaded with ManICS1-AM show changes in MRI contrast when stimulated with pharmacological agents or optogenetic tools; responses directly parallel the signals obtained using fluorescent calcium indicators. Introduction of ManICS1-AM into rodent brains furthermore permits MRI-based measurement of neural activation in optically inaccessible brain regions. These results thus validate ManICS1-AM as a calcium sensor compatible with the extensive penetration depth and field of view afforded by MRI.