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Updated: Aug 1, 2026
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Imaging Membrane Potential with Two Types of Genetically Encoded Fluorescent Voltage Sensors
Published on: February 4, 2016
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Electrophysiology, Unplugged: Imaging Membrane Potential with Fluorescent Indicators
Accounts of Chemical Research
|December 14, 2019
Summary
Researchers developed novel voltage-sensitive fluorescent dyes (VoltageFluors) for observing cellular membrane potential dynamics. These VoltageFluors offer a faster, more sensitive optical method to monitor electrical activity in neurons and other cells.
Area of Science:
- Biophysics
- Neuroscience
- Chemical Biology
- Optical Imaging
Background:
- Cellular membrane potential is crucial for neuronal function, cognition, and sensory perception.
- Traditional electrode-based methods for measuring membrane potential are invasive and provide limited system-wide data.
- Voltage-sensitive fluorescent indicators offer a non-invasive optical alternative for monitoring dynamic membrane potential changes.
Purpose of the Study:
- To design, synthesize, and apply novel voltage-sensitive fluorophores (VoltageFluors) for sensitive and rapid reporting of membrane potential dynamics.
- To overcome limitations of existing voltage-sensing techniques by developing advanced optical indicators.
- To enable direct observation of membrane potential changes in living systems with high spatiotemporal resolution.
Main Methods:
- Development of VoltageFluors based on membrane potential-dependent photoinduced electron transfer (PeT).
- Utilized a design strategy involving a fluorophore, a conjugated molecular wire, and an aniline donor.
- Tested various fluorophore, molecular wire, and aniline donor combinations to optimize dye performance.
Main Results:
- Successfully generated fast (∼25 ns response kinetics) and sensitive (>60% ΔF/F) VoltageFluor dyes.
- Demonstrated compatibility with two-photon illumination, excellent signal-to-noise ratios, and ability to detect neuronal and cardiac action potentials in single trials.
- Showcased application of advanced VoltageFluors, including silicon rhodamine and carbofluorescein-based indicators, for two-photon voltage imaging in intact brains.
Conclusions:
- The developed VoltageFluors provide a powerful optical tool for monitoring membrane potential dynamics with high sensitivity and speed.
- The PeT-based mechanism enables fast and reliable voltage sensing, complementing traditional electrophysiological methods.
- Future opportunities include developing hybrid indicators for targeted cell imaging and addressing remaining challenges in voltage imaging.
