- Author:
- WeiweiAi <wai484@aucklanduni.ac.nz>
- Date:
- 2021-05-10 15:58:10+12:00
- Desc:
- Add documentation
- Permanent Source URI:
- https://models.cellml.org/workspace/64f/rawfile/c177badb5a6ff1ec89413c178ecadb5a2e759a44/doc/README.rst
===================
About this model
===================
:Original publication: `Hodgkin & Huxley (1952)`_: ‘A Quantitative Description of Membrane Current and its Application to Conduction and Excitation in Nerve’, J. Physiol. 117: 500-544.
:DOI: https://doi.org/10.1113/jphysiol.1952.sp004764
.. _`Hodgkin & Huxley (1952)`: http://www.ncbi.nlm.nih.gov/pubmed/12991237
Model overview
===================
This workspace holds a CellML_ encoding of the `Hodgkin & Huxley (1952)`_ model.
The `Hodgkin & Huxley (1952)`_ (HH) model is one of the foundational models of cellular electrophysiology.
It defined the “standard” gating kinetics still used in many models today.
The model includes potassium, sodium, and ‘leakage’ currents as well and the transmembrane electrical potential.
The HH model was originally developed to investigate flow of electric charge in giant nerve axons in squid.
.. image:: ./math-overview.png
:width: 85%
:align: center
:alt: Schematics of the model
.. _CellML: https://www.cellml.org/
Modular description
===================
Components
----------
CellML divides the mathematical model into distinct components, which are able to be re-used.
The main CellML components are:
- `Membrane potential component <../components/stimulated.cellml/view>`_
- `Membrane current component <../components/clamped_current.cellml/view>`_ (the ionic current during a voltage clamp)
- `Propagated action potential component <../components/propagated_AP.cellml/view>`_
- `Potassium current component <../components/IK.cellml/view>`_
- `Sodium current component <../components/INa.cellml/view>`_
- `Leakage current component <../components/Ileak.cellml/view>`_
- `Gating kinetics component <../components/gating-variable.cellml/view>`_ – a single definition instantiated three times for the n, m, and h gates
- `Gating rates components <../components/IK-gating-rates.cellml/view>`_ (open/close rates for n, m, and h gates respectively)
- `Gate initialization components <../components/gate_initials.cellml/view>`_ (steady state values of n, m, and h gates under voltage boundary condition)
- `Temperature component <../experiments/time.cellml/view>`_
Each of these blocks is itself a CellML model, which enables us to reuse the various components in future studies and models.
Experiments protocols
---------------------
Following best practices, this model separates the mathematics from the parameterisation of the model. The mathematical model is imported into a specific parameterised instance in order to perform numerical simulations.
The parameterisation would include defining the stimulus protocol to be applied.
This workspace has three sets of experiments:
1. `Periodic stimulation <../experiments/periodic-stimulus.cellml/view>`_:
The model is configured and parameterised with an applied `periodic current stimulus <../experiments/periodic stimulus current <periodic-IStim-protocol.cellml>`_. The simulation experiment can be obtained by loading the `corresponding SED-ML document <../sed-ml/periodic-stimulus.sedml>`__ into OpenCOR and executing the simulation.
2. `Voltage clamp experiment <../experiments/voltage_clamp_experiment.cellml/view>`_:
The model is configured and parameterised to simulate the behaviour during a `voltage clamp <../experiments/voltage_clamp_protocol.cellml>`_. The simulation experiment can be obtained by loading the `corresponding SED-ML document <../sed-ml/voltage_clamp_experiment.sedml>`__ into OpenCOR and executing the simulation.
3. `Action potential propagation along 1D cable model <../experiments/AP_propagation_experiment.cellml/view>`_ (please see Known issues):
The model is configured and parameterised to simulate a propagated action potential. The simulation experiment can be obtained by loading the `corresponding SED-ML document <../sed-ml/AP_propagation_experiment.sedml>`__ into OpenCOR and executing the simulation.
Simulation settings
-------------------
Simulation settings are encoded in SED-ML_ documents for experiment execution.
The python scripts to run simulation and reproduce the figures in the original paper are also included.
.. _SED-ML: http://sed-ml.org/
Model history
===================
The original model implementation is from `VPH-MIP case study`_. The main modification is summarized as follows:
1. Add the temperature component to simulate the model at different temperatures.
2. Add clamped_current.cellml, voltage_clamp_protocol.cellml and voltage_clamp_experiment.cellml to simulate a membrane current during a voltage clamp.
3. Add propagated_AP.cellml and AP_propagation_experiment.cellml to simulate propagated action potential.
4. Add the python scripts to run simulation and reproduce the figures in the original paper.
.. _`VPH-MIP case study`: https://models.physiomeproject.org/w/andre/VPH-MIP
Known issues
===================
1. The voltage clamp value cannot be -10 mV as the :math:`\alpha_n` would be infinity.
2. The propagated action potential model does not work, which needs further investigation in future.
3. The temperature unit is set to Kelvin in the CellML models. If you want to simulate the model behavior at temperature T with unit Celsius, you do not need to do conversion as the offset is cancelled in the mathematical expressions including temperature factor.
4. You need to set appropriate parameters and initial values in the CellML files, if you want to run simulation using OpenCOR_ rather than the provided Python scripts.
.. _OpenCOR: https://opencor.ws/
