Extended voltage imaging in cardiomyocytes with a triplet state quencher-stabilized silicon rhodamine

Kayli N. Martinez; Nels C. Gerstner; Samantha J. Yang; Evan W. Miller

doi:10.1016/j.bmcl.2024.129842

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Extended voltage imaging in cardiomyocytes with a triplet state quencher-stabilized silicon rhodamine

Journal article

Peer reviewed

Extended voltage imaging in cardiomyocytes with a triplet state quencher-stabilized silicon rhodamine

Kayli N. Martinez, Nels C. Gerstner, Samantha J. Yang and Evan W. Miller

Bioorganic & medicinal chemistry letters, Vol.109(C), p.129842

09/01/2024

DOI: 10.1016/j.bmcl.2024.129842

PMCID: PMC11648968

PMID: 38844174

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https://pmc.ncbi.nlm.nih.gov/articles/PMC11648968/pdf/nihms-2005831.pdfView

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Abstract

[Display omitted] Voltage imaging of cardiac electrophysiology with voltage-sensitive dyes has long been a powerful complement to traditional methods like patch-clamp electrophysiology. Chemically synthesized voltage sensitive fluorophores offer flexibility for imaging in sensitive samples like human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs), since they do not require genetic transformation of the sample. One serious concern for any fluorescent voltage indicator, whether chemically synthesized or genetically encoded, is phototoxicity. We have been exploring self-healing fluorophores that use triplet state quenchers (TSQs) as a means to reduce the already low phototoxicity of VoltageFluor dyes developed in our lab. We previously showed that conjugation of the TSQ cyclooctatetraene (COT) to a fluorescein based VoltageFluor dye substantially reduced phototoxicity. Here, we show that this approach can be applied to far-red Silicon rhodamine dyes. COT-conjugated Si-rhodamines show improved photostability and reduced phototoxicity in hiPSC-CMs compared to the unmodified dye. This enables imaging of hiPSC-CMs for up to 30 min with continuous illumination. We show that this effect is mediated by a combination of reduced singlet oxygen production and lower loading in the cellular membrane. We discuss future applications and avenues of improvement for TSQ-stabilized VoltageFluor dyes.

Fluorescence microscopy

Triplet-state quenchers

Voltage imaging

Details

Title: Subtitle: Extended voltage imaging in cardiomyocytes with a triplet state quencher-stabilized silicon rhodamine
Creators: Kayli N. Martinez - University of California, Berkeley
Nels C. Gerstner - University of California, Berkeley
Samantha J. Yang - University of California, Berkeley
Evan W. Miller - University of California, Berkeley
Resource Type: Journal article
Publication Details: Bioorganic & medicinal chemistry letters, Vol.109(C), p.129842
DOI: 10.1016/j.bmcl.2024.129842
PMID: 38844174
PMCID: PMC11648968
NLM abbreviation: Bioorg Med Chem Lett
ISSN: 0960-894X
eISSN: 1464-3405
Publisher: Elsevier Ltd
Language: English
Date published: 09/01/2024
Academic Unit: Chemistry
Record Identifier: 9984934816802771

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