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Modelling patch-clamp experiments

When analysing data from whole-cell patch-clamp experiments, it can be useful to have a model of both the biological system of interest and the experimental set up. In these notebooks we retrace the steps taken in the supplement to Lei et al., 2020, and construct (1) a model of a patch-clamp experiment with various experimental artefacts, and (2) a model of the corrections applied by patch-clamp amplifiers to mitigate these effects. The exposition draws heavily on a book chapter by Sigworth (1995a).

I have tried to keep things as to-the-point as possible, but a lot of extra detail is provided in the appendices.

Modelling patch-clamp experiments github nbviewer

The first notebook describes the uncompensated patch-clamp set up, and shows how to derive both an electrical schematic and an ODE model.

Modelling electronic compensation github nbviewer

In the second notebook we update the model to include the compensation circuitry commonly used in patch-clamp amplifiers.

Modelling filters github nbviewer

(Unfinished) In this notebook, we walk through the steps of a manual patch-clamp experiment.

Simulating a manual patch clamp experiment github nbviewer

(Unfinished) In this notebook, we walk through the steps of a manual patch-clamp experiment.

Simplified models github nbviewer

(Unfinished) In notebook number five we derive simplified models of the compensated voltage clamp setup, which can be used in fitting.

Summary github nbviewer

(Unfinished) Finally, we present two simplified models (with currents in pA and currents in A/F), in equation & Myokit form.

Appendices

  • Electronics
    • A1. Ideal op amps github nbviewer
    • A2. Laplace transforms and filters github nbviewer
    • A3. Non-ideal op amps github nbviewer
    • A4. Bessel low-pass filters github nbviewer
    • A5. Bessel filter ODEs github nbviewer
  • Extended models
    • B1. Models without compensation github nbviewer
    • B2. Models with compensation github nbviewer
    • B3. Sigworth 1983/1995 Rs compensation github nbviewer
  • Parameter names and values
    • C1. Names & symbols github nbviewer
    • C2. Default parameter values used in examples github nbviewer
    • C3. Parameter values, estimates for different amplifiers etc. github nbviewer
  • Remaining noise and errors
    • D1. Strategies for dealing with experimental error github nbviewer
    • D2. Stochastic and periodic noise github nbviewer
    • D3. Liquid junction potential github nbviewer
    • D4. Leak (unfinished) github nbviewer
    • D5. Handling remaining capacitance artefacts (unfinished) github nbviewer
  • Estimating Rs and Cm
    • E1. Estimating Rs and Cm; a one-shot approach github nbviewer
    • E2. Estimating Rs and Cm; an iterative approach github nbviewer