Improved PeT molecules for optically sensing voltage in neurons

J Am Chem Soc. 2015 Feb 11;137(5):1817-24. doi: 10.1021/ja510602z. Epub 2015 Jan 29.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Drug Design
  • Electron Transport
  • Electrophysiological Phenomena*
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry*
  • HEK293 Cells
  • Humans
  • Light*
  • Membrane Potentials
  • Mice
  • Neurons / chemistry
  • Neurons / cytology*
  • Olfactory Bulb / cytology
  • Optical Imaging
  • Optical Phenomena*
  • Rats

Substances

  • Fluorescent Dyes