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

81 Scopus citations

Abstract

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
Volume137
Issue number5
DOIs
StatePublished - Feb 11 2015
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Fingerprint

Dive into the research topics of 'Improved PeT molecules for optically sensing voltage in neurons'. Together they form a unique fingerprint.

Cite this