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Novel far-red fluorescent 1,4-dihydropyridines for L-type calcium channel imaging

13 February 2024, Version 2

Abstract

Upregulation of L-type calcium channels (LTCCs) is implicated in a range of cardiovascular and neurological disorders. Therefore, the development of toolboxes that unlocks fast imaging protocols in live cells are coveted. Herein, we report a library of first-in-class novel far-red small-molecule-based fluorescent ligands (FluoDiPines), able to target LTCCs. All fluorescent ligands were evaluated in whole-cell patch-clamp and live-cell Ca2+ imaging whereby Fluodipine 6 was found the best candidate for live-cell fluorescence imaging. Low concentration of FluoDiPine 6 (50 nM) and a quick labelling protocol (5 min) are successfully applied to fixed- and live-cells to image LTCCs with good specificity.

Keywords

L-type calcium channels
Ion channels
Live-cell imaging
Confocal
Fluorescence imaging
Calcium channel blockers

Supplementary materials

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Supplementary materials
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Supporting information includes: biological protocols, synthetic protocols and compound characterization.
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Version History

Feb 13, 2024 Version 2

Version Notes

The text underwent formatting changes for improvement.

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The content is available under CC BY NC ND 4.0 [opens in a new tab]

DOI

10.26434/chemrxiv-2023-5z0lq-v2
D O I: 10.26434/chemrxiv-2023-5z0lq-v2 [opens in a new tab]

Funding

FWO-SB fellowship
1SB6521N-1SB6523N
FWO-SB fellowship
1S50320N
FWO
I001818N and I001719N
KU Leuven
IDN/19/039
MSCA-SoE-FWO fellowship
12Z6620N
Gipuzkoa Fellows Programs
2022-000013-01
Research Council Ku Leuven
C14/19/099 and AKUL/19/34
FWO-WOG CaSign
W001422N
FWO
G066821N
INTERREG – Euregio Meuse-Rhine
2020-EMR116
Italian Ministry of Health
RF-2019-12369703
FWO Infrastructure
I002720N and I001920N
Hercules Foundation of the Flemish Government
20100225–7
FWO
G081821N

Author’s competing interest statement

The author(s) have declared they have no conflict of interest with regard to this content

Ethics

The author(s) declare that they have sought and gained approval from the relevant ethics committee/IRB for this research and its publication.

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