Voltage clamp model

This repository contains up-to-date reference versions of the voltage clamp model developed in Lei et al. 2020 and 2025. These models can be used to simulate manual or planar patch-clamp experiments in voltage-clamp mode.

Note: This URL originally hosted data and code for the 2020 Lei et al. publication. This is now found at https://github.com/CardiacModelling/VoltageClampModel2020

The latest models

We recently updated the voltage clamp model with improved filtering of input (stimulus filter) and output, and an improved time-delay in the series resistance compensation pathway.

In addition to this full-featured model, we provide a set of increasingly simplified models:

• The "Level 0" model includes all features.
• "Level 1" simplifies this by replacing all filters with first-order approximations.
• "Level 2" further assumes an ideal measuring op-amp without stray capacitance.
• "Level 3" removes fast capacitance currents and their correction.
• "Level 4" removes all filtering entirely.
• "Level 5" assumes perfect slow capacitance cancellation (but imperfect series resistance compensation).

All models are provided in Myokit (models-mmt) and CellML (models-cellml-v1) formats.

Which model should I use?

The Model Tour provides a quick overview of levels 5, 4, 3, and 0, including schematics, equations, and parameter values.

In brief:

• Levels 0, 1, and 2 can recreate the fast artefacts seen in patch clamp experiments, and are very useful to understand the patch clamp process.
• To fit experimental data, these fast artefacts are less important, and so level 3 is good to match data from the fastest currents. For slower currents, levels 4 or 5 can be used.

Tutorials

We provide four Tutorial Notebooks to understand these models, and how they were derived.

The first notebook establishes a basic model of a patch clamp amplifier, and the second adds compensation and filtering, leading to the "Level 0" model. In the third notebook, this model is used to simulate a manual patch-clamp experiment.

The final notebook derives the Level 1 to 5 simplifications, and shows how they relate to our previous work (Lei et al., 2020 and 2025).

Previous versions

Lei et al. 2020

The first published version was in

Accounting for variability in ion current recordings using a mathematical model of artefacts in voltage-clamp experiments. Lei, C.L., Clerx, M., Whittaker, D.G., Gavaghan D.J., de Boer, T.P. and Mirams, G.R. (2020). Philosophical Transactions of the Royal Society A, 378: 20190348. https://doi.org/10.1098/rsta.2019.0348

BibTeX entry:

@article{Lei2020Variability,
  author = {Lei, Chon Lok  and Clerx, Michael  and Whittaker, Dominic G.  and Gavaghan, David J.  and de Boer, Teun P.  and Mirams, Gary R. },
  title = {Accounting for variability in ion current recordings using a mathematical model of artefacts in voltage-clamp experiments},
  journal = {Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences},
  volume = {378},
  number = {2173},
  pages = {20190348},
  year = {2020},
  doi = {10.1098/rsta.2019.0348}
}

Code: https://github.com/CardiacModelling/nav-artefact-model

Lei et al. 2025

The "supercharging" or "prediction" pathway was added in

Resolving Artifacts in Voltage-Clamp Experiments with Computational Modeling: An Application to Fast Sodium Current Recordings. Lei, C.L., Clark, A.P., Clerx, M., Wei, S., Bloothooft, M., de Boer, T.P., Christini, D.J., Krogh-Madsen, T., and Mirams, G.R. (2025). Advanced Science, 12, 30: e00691. https://doi.org/10.1002/advs.202500691

BibTeX entry:

@article{Lei2025Artifacts,
  author = {Lei, Chon Lok and Clark, Alexander P. and Clerx, Michael and Wei, Siyu and Bloothooft, Meye and de Boer, Teun P. and Christini, David J. and Krogh-Madsen, Trine and Mirams, Gary R.},
  title = {Resolving Artifacts in Voltage-Clamp Experiments with Computational Modeling: An Application to Fast Sodium Current Recordings},
  journal = {Advanced Science},
  volume = {12},
  number = {30},
  pages = {e00691},
  year = {2025},
  doi = {https://doi.org/10.1002/advs.202500691}
}

Code: https://github.com/CardiacModelling/VoltageClampModel2020

Acknowledging this work

If you use the contents of this repository in your work, please cite the papers listed above.