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Quantifying the efficacy of voltage protocols in characterising ion channel kinetics: A novel information‐theoretic approach
,
Sanjay Pant
International Journal for Numerical Methods in Biomedical Engineering, Volume: 40, Issue: 5
Swansea University Authors:
Matthew Jennings, Perumal Nithiarasu , Sanjay Pant
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DOI (Published version): 10.1002/cnm.3815
Abstract
Voltage-clamp experiments are commonly utilised to characterise cellular ion channel kinetics. In these experiments, cells are stimulated using a known time-varying voltage, referred to as the voltage protocol, and the resulting cellular response, typically in the form of current, is measured. Param...
| Published in: | International Journal for Numerical Methods in Biomedical Engineering |
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| ISSN: | 2040-7939 2040-7947 |
| Published: |
Wiley
2024
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa65810 |
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| Abstract: |
Voltage-clamp experiments are commonly utilised to characterise cellular ion channel kinetics. In these experiments, cells are stimulated using a known time-varying voltage, referred to as the voltage protocol, and the resulting cellular response, typically in the form of current, is measured. Parameters of models that describe ion channel kinetics are then estimated by solving an inverse problem which aims to minimise the discrepancy between the predicted response of the model and the actual measured cell response. In this paper, a novel framework to evaluate the information content of voltage-clamp protocols in relation to ion channel model parameters is presented. Additional quantitative information metrics that allow for comparisons among various voltage protocols are proposed. These metrics offer a foundation for future optimal design frameworksto devise novel, information-rich protocols. The efficacy of the proposed framework is evidenced through the analysis of seven voltage protocols from the literature. By comparing known numerical results for inverse problems using these protocols with the information-theoretic metrics, the proposed approach is validated. The essential steps of the framework are: (i) generate random samples of the parameters from chosen prior distributions; (ii) run the model to generate model output (current) for all samples; (iii) construct reduceddimensional representations of the time-varying current output using Proper Orthogonal Decomposition (POD); (iv) estimate information-theoretic metrics such as mutual information, entropy equivalent variance, and conditional mutual information using non-parametric methods; (v) interpret the metrics; for example, a higher mutual information between a parameter and the current output suggests the protocol yields greaterinformation about that parameter, resulting in improved identifiability; and (vi) integrate the informationtheoretic metrics into a single quantitative criterion, encapsulating the protocol’s efficacy in estimating model parameters. |
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| Keywords: |
Information theory, Experimental design, Ion channel kinetics, Parameter estimation, Identifiability |
| College: |
Faculty of Science and Engineering |
| Funders: |
MJ acknowledges the support of EPSRC Standard Research Studentship (DTP) for this work. |
| Issue: |
5 |