Journal article
A parameter representing missing charge should be considered when calibrating action potential models
- Abstract:
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Computational models of the electrical potential across a cell membrane are longstanding and vital tools in electrophysiology research and applications. These models describe how ionic currents, internal fluxes, and buffering interact to determine membrane voltage and form action potentials (APs). Although this relationship is usually expressed as a differential equation, previous studies have shown it can be rewritten in an algebraic form, allowing direct calculation of membrane voltage. Rewriting in this form requires the introduction of a new parameter, called Γ0 in this manuscript, which represents the net concentration of all charges that influence membrane voltage but are not considered in the model. Although several studies have examined the impact of Γ0 on long-term stability and drift in model predictions, there has been little examination of its effects on model predictions, particularly when a model is refit to new data. In this study, we illustrate how Γ0 affects important physiological properties such as action potential duration restitution, and examine the effects of (in)correctly specifying Γ0 during model calibration. We show that, although physiologically plausible, the range of concentrations used in popular models leads to orders of magnitude differences in Γ0, which can lead to very different model predictions. In model calibration, we find that using an incorrect value of Γ0 can lead to biased estimates of the inferred parameters, but that the predictive power of these models can be restored by fitting Γ0 as a separate parameter. These results show the value of making Γ0 explicit in model formulations, as it forces modellers and experimenters to consider the effects of uncertainty and potential discrepancy in initial concentrations upon model predictions.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Version of record, pdf, 2.9MB, Terms of use)
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- Publisher copy:
- 10.3389/fphys.2022.879035
Authors
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Physiology More from this journal
- Volume:
- 13
- Article number:
- 879035
- Publication date:
- 2022-04-26
- Acceptance date:
- 2022-03-16
- DOI:
- EISSN:
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1664-042X
- Pmid:
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35557969
- Language:
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English
- Keywords:
- Pubs id:
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1259644
- Local pid:
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pubs:1259644
- Deposit date:
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2023-10-19
Terms of use
- Copyright holder:
- Barral et al.
- Copyright date:
- 2022
- Rights statement:
- Copyright © 2022 Barral, Shuttleworth, Clerx, Whittaker, Wang, Polonchuk, Gavaghan and Mirams. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Notes:
- This research was funded in whole, or in part, by the Wellcome Trust (212203/Z/18/Z). For the purpose of open access, the author has applied a CC-BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
- Licence:
- CC Attribution (CC BY)
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