ArticlePhilosophical transactions. Series A, Mathematical, physical, and engineering sciences2020
Accounting for variability in ion current recordings using a mathematical model of artefacts in voltage-clamp experiments.
Article in Philosophical transactions. Series A, Mathematical, physical, and engineering sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Variability in reported midpoints of (in)activation of cardiac INa.The Journal of general physiology · 2025Pooled it
- Article
- Large-scale synthetic data enable digital twins of human excitable cells.bioRxiv : the preprint server for biology · 2025Article
- Resolving Artifacts in Voltage-Clamp Experiments with Computational Modeling: An Application to Fast Sodium Current Recordings.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Parameter inference for stochastic reaction models of ion channel gating from whole-cell voltage-clamp data.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2025Article
- Evaluating the predictive accuracy of ion-channel models using data from multiple experimental designs.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2025Article
- KbioRxiv : the preprint server for biology · 2025Article
- Single-cell ionic current phenotyping elucidates non-canonical features and predictive potential of cardiomyocytes during automated drug experiments.The Journal of physiology · 2024Article
- Stem cell-derived cardiomyocyte heterogeneity confounds electrophysiological insights.The Journal of physiology · 2024Review
- Single-cell ionic current phenotyping explains stem cell-derived cardiomyocyte action potential morphology.American journal of physiology. Heart and circulatory physiology · 2024Article
- Membrane-coated glass electrodes for stable, low-noise electrophysiology recordings in Drosophila central neurons.Journal of neuroscience methods · 2024Article
- A range of voltage-clamp protocol designs for rapid capture of hERG kinetics.Wellcome open research · 2024Article
- Empirical Quantification of Predictive Uncertainty Due to Model Discrepancy by Training with an Ensemble of Experimental Designs: An Application to Ion Channel Kinetics.Bulletin of mathematical biology · 2023Article
- Uncertainty assessment of proarrhythmia predictions derived from multi-level in silico models.Archives of toxicology · 2023Article
- Leak current, even with gigaohm seals, can cause misinterpretation of stem cell-derived cardiomyocyte action potential recordings.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2023Article
- A need for exhaustive and standardized characterization of ion channels activity. The case of KFrontiers in physiology · 2023Review
- Models of the cardiac L-type calcium current: A quantitative review.WIREs mechanisms of disease · 2023Review
- An in silico-in vitro pipeline for drug cardiotoxicity screening identifies ionic pro-arrhythmia mechanisms.British journal of pharmacology · 2022Article
- Article
- Electrophysiological characterization of the hERG R56Q LQTS variant and targeted rescue by the activator RPR260243.The Journal of general physiology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Mathematical models of ion channels, which constitute indispensable components of action potential models, are commonly constructed by fitting to whole-cell patch-clamp data. In a previous study, we fitted cell-specific models to hERG1a (Kv11.1) recordings simultaneously measured using an automated high-throughput system, and studied cell-cell variability by inspecting the resulting model parameters. However, the origin of the observed variability was not identified. Here, we study the source of variability by constructing a model that describes not just ion current dynamics, but the entire voltage-clamp experiment. The experimental artefact components of the model include: series resistance, membrane and pipette capacitance, voltage offsets, imperfect compensations made by the amplifier for these phenomena, and leak current. In this model, variability in the observations can be explained by either cell properties, measurement artefacts, or both. Remarkably, by assuming that variability arises exclusively from measurement artefacts, it is possible to explain a larger amount of the observed variability than when assuming cell-specific ion current kinetics. This assumption also leads to a smaller number of model parameters. This result suggests that most of the observed variability in patch-clamp data measured under the same conditions is caused by experimental artefacts, and hence can be compensated for in post-processing by using our model for the patch-clamp experiment. This study has implications for the question of the extent to which cell-cell variability in ion channel kinetics exists, and opens up routes for better correction of artefacts in patch-clamp data. This article is part of the theme issue 'Uncertainty quantification in cardiac and cardiovascular modelling and simulation'.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.