Improved PeT molecules for optically sensing voltage in neurons

Clifford R. Woodford, E. Paxon Frady, Richard S. Smith, Benjamin Morey, Gabriele Canzi, Sakina F. Palida, Ricardo C. Araneda, William B. Kristan, Clifford P. Kubiak, Evan W. Miller*, Roger Y. Tsien

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


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 (ΔGPeT + w) through systematic chemical substitution modulates voltage sensitivity, estimate (ΔGPeT + 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% ΔF/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.

Original languageEnglish (US)
Pages (from-to)1817-1824
Number of pages8
JournalJournal of the American Chemical Society
Issue number5
StatePublished - Feb 11 2015

ASJC Scopus subject areas

  • General Chemistry
  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry


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