Quantifying the efficacy of voltage protocols in characterising ion channel kinetics: A novel information-theoretic approach.

Publisher: Wiley Country of Publication: England NLM ID: 101530293 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2040-7947 (Electronic) Linking ISSN: 20407939 NLM ISO Abbreviation: Int J Numer Method Biomed Eng Subsets: MEDLINE

Original Publication: [Oxford, UK] : Wiley

Ion Channels*/metabolism; Kinetics ; Patch-Clamp Techniques ; Information Theory ; Algorithms ; Models, Biological ; Humans

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 frameworks to 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 reduced-dimensional 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 greater information about that parameter, resulting in improved identifiability; and (vi) integrate the information-theoretic metrics into a single quantitative criterion, encapsulating the protocol's efficacy in estimating model parameters.
(© 2024 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

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2600792 Engineering and Physical Sciences Research Council

Keywords: experimental design; identifiability; information theory; ion channel kinetics; parameter estimation

0 (Ion Channels)

Date Created: 20240328 Date Completed: 20240514 Latest Revision: 20260203

20260203

10.1002/cnm.3815

38544355