Voltage-Clamp Experiment Model

A detailed mathematical model of a voltage-clamp experiment with imperfect patch-clamp amplifier compensations

Release Notes

March 2021

The latest version of this repository includes supercharging compensation, following the equations in Chapter 6 of Chon Lok Lei's thesis.

April 2020

This repo contains all data and code for reproducing the results in the paper "Accounting for variability in ion current recordings using a mathematical model of artefacts in voltage-clamp experiments" by Chon Lok Lei, Michael Clerx, Dominic Whittaker, David Gavaghan, Teun de Boer, and Gary Mirams. doi:10.1098/rsta.2019.0348. A permanently archived version (without supercharging) for reproducing the results in the paper is available as a tagged release or on Zenodo at https://doi.org/10.5281/zenodo.3754184.

Installing

To run the code to generate the data and figures shown in the paper, please follow these steps first:

1. Clone hERGRapidCharacterisation to the relative path ../hERGRapidCharacterisation.
2. To setup, either run (for Linux/macOS users)

$ bash setup.sh

or install PINTS and Myokit manually with Python 3.5+.

Results

Section 3: Validating the mathematical model with electrical model cell experiments

• model-cell-experiments: Application of the voltage-clamp experiment model to electrical model cell experiments.
  • contains results and code to reproduce Figures 4, 5; Table 2; Figures S4, S5; Tables S1, S2.

Section 4: Application to variability in CHO-hERG1a patch-clamp data

• herg-syn-study: Synthetic studies with the voltage-clamp experiment model.

  • contains results and code to reproduce Figure S6.

• herg-real-data: Application of the voltage-clamp experiment model to data in hERGRapidCharacterisation.

  • Contains results and code to reproduce Hypothesis 2: Figures 7, 8; Figures S7, S8, S9; Tables S3, S4.
  • Also contains results and code that are mentioned but not shown in the paper: full voltage-clamp experiment model fitting to hERG data; independent kinetics with independent artefacts 'Hypothesis 3'.

Supporting files

• lib: Contains all modules/utility functions.

• mmt-model-files: Myokit model files, contains IKr model and voltage clamp experiment model etc.

• protocol-time-series: Contains protocols as time series, stored as .csv files, with time points (in s) and voltage (in mV)

• data, data-autoLC, manualselection, qc: symbolic links to hERGRapidCharacterisation

• cellml: CellML version of the models in mmt-model-files.

Acknowledging this work

If you publish any work based on the contents of this repository please cite (CITATION file):

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