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Sensing intracellular calcium ions using a manganese-based MRI contrast agent
Name
s41467-019-08558-7.pdf
Description
Published version
Size
1.17 MB
Format
Adobe PDF
Checksum (MD5)
b1bd2c4bd4802ccd976d97770efc32a3
Author(s)
Barandov, Ali
Bartelle, Benjamin B
Williamson, Catherine G
Loucks, Emily S
Lippard, Stephen J
Jasanoff, Alan
Date Issued
2019
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Version
Final published version
Abstract
© 2019, The Author(s). 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.
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
10.1038/S41467-019-08558-7
