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Exploring Sub-Microsecond Plasma Membrane Potential Shifts and Bioeffects Under Low-Energy Electric Pulse Stimulation
Gleb P Tolstykh1, Mark A Keppler2, Roberto A Rodriguez3
1JBSA Fort Sam Houston, General Dynamics Information Technology, San Antonio, Texas, USA.
Bioelectricity
|July 6, 2026
Summary
Low-energy electric pulses (EPs) can depolarize cell membranes. Nanosecond EP bursts, unlike single pulses, charge membranes through temporal summation, inducing calcium responses in neurons without cell damage.
Area of Science:
- Biophysics
- Cellular Electrophysiology
Background:
- Micro- and millisecond electric pulses (EPs) depolarize cellular plasma membranes (PM) below electroporation thresholds.
- Individual nanosecond EPs (NSEPs) are too brief to depolarize cells via PM charging.
Purpose of the Study:
- To investigate the effects of low-energy nanosecond EP bursts on cellular PM depolarization.
- To compare the efficacy of NSEP bursts versus single microsecond EPs in inducing PM depolarization and calcium influx.
Main Methods:
- Utilized optical measurements with FluoVolt™ (a membrane potential reporter) and a streak imaging system.
- Applied single 200 µs EPs and 5 MHz trains of 1000 and 2000 NSEPs (100 ns duration) at ~0.2 kV/cm.
- Recorded ultra-fast streak kymographs to visualize PM voltage changes.
Main Results:
- Observed small PM fluorescence changes (up to ~7%) following EP exposure, correlating with pulse width or burst interval.
- Single 200 µs EPs were more effective at PM charging than equivalent-energy 2000 NSEP bursts.
- Increasing pulse width or voltage was necessary to enhance PM depolarization; however, modest depolarization opened voltage-gated Ca2+ channels in neurons.
Conclusions:
- Low-energy 5 MHz NSEP bursts and single µs EPs effectively induce PM depolarization and Ca2+ responses.
- These methods achieve cellular effects without causing observable cellular damage.
- Temporal summation of NSEPs offers a viable strategy for non-damaging cellular membrane manipulation.
