Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 137, Issue 5, Pages 1817-1824Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja510602z
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Funding
- Howard Hughes Medical Institute
- NIH [R37NS027177, MH43396, EB009380, MH020002, DC009817]
- Pathways to Independence Award [K99/R00NS078561]
- NSF [IOB-0523959, CHE-1145893]
- AFOSR FA [9550-13-1-0020]
- Division Of Chemistry
- Direct For Mathematical & Physical Scien [1145893] Funding Source: National Science Foundation
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VoltageFluor (VF) dyes have the potential to measure voltage optically in excitable membranes with a combination of high spatial and temporal resolution essential to better characterize the voltage dynamics of large groups of excitable cells. VF dyes sense voltage with high speed and sensitivity using photoinduced electron transfer (PeT) through a conjugated molecular wire. We show that tuning the driving force for PeT (Delta G(PeT) + w) through systematic chemical substitution modulates voltage sensitivity, estimate (Delta G(PeT) + w) values from experimentally measured redox potentials, and validate the voltage sensitivities in patch-clamped HEK cells for 10 new VF dyes. VF2.1(OMe).H, with a 48% Delta F/F per 100 mV, shows approximately 2-fold improvement over previous dyes in HEK cells, dissociated rat cortical neurons, and medicinal leech ganglia. Additionally, VF2.1(OMe).H faithfully reports pharmacological effects and circuit activity in mouse olfactory bulb slices, thus opening a wide range of previously inaccessible applications for voltage-sensitive dyes.
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