ArticleBiophysical journal2019
Rapid Characterization of hERG Channel Kinetics I: Using an Automated High-Throughput System.
Article in Biophysical journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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.
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Who cites it
28 citing papers in PubMed, 60 citations in OpenAlex.
- Discovery of a novel broad-spectrum inhibitor against influenza virus A.Virology journal · 2025Article
- IonBench: A benchmark of optimisation strategies for mathematical models of ion channel currents.PLoS computational biology · 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
- 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
- Single-cell ionic current phenotyping elucidates non-canonical features and predictive potential of cardiomyocytes during automated drug experiments.The Journal of physiology · 2024Article
- Recording ten-fold larger IFrontiers in physiology · 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
- Models of the cardiac L-type calcium current: A quantitative review.WIREs mechanisms of disease · 2023Review
- A need for exhaustive and standardized characterization of ion channels activity. The case of KFrontiers in physiology · 2023Review
- Improving the hERG model fitting using a deep learning-based method.Frontiers in physiology · 2023Article
- Ion channel model reduction using manifold boundaries.Journal of the Royal Society, Interface · 2022Article
- A Quantitative Systems Pharmacology Perspective on the Importance of Parameter Identifiability.Bulletin of mathematical biology · 2022Article
- A standardised hERG phenotyping pipeline to evaluate KCNH2 genetic variant pathogenicity.Clinical and translational medicine · 2021Article
- Electrophysiological characterization of the hERG R56Q LQTS variant and targeted rescue by the activator RPR260243.The Journal of general physiology · 2021Article
- Identification of structures for ion channel kinetic models.PLoS computational biology · 2021Article
- Computational and experimental studies on the inhibitory mechanism of hydroxychloroquine on hERG.Toxicology · 2021Article
- Article
- Neural Network Differential Equations For Ion Channel Modelling.Frontiers in physiology · 2021Article
- Calibration of ionic and cellular cardiac electrophysiology models.Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Predicting how pharmaceuticals may affect heart rhythm is a crucial step in drug development and requires a deep understanding of a compound's action on ion channels. In vitro hERG channel current recordings are an important step in evaluating the proarrhythmic potential of small molecules and are now routinely performed using automated high-throughput patch-clamp platforms. These machines can execute traditional voltage-clamp protocols aimed at specific gating processes, but the array of protocols needed to fully characterize a current is typically too long to be applied in a single cell. Shorter high-information protocols have recently been introduced that have this capability, but they are not typically compatible with high-throughput platforms. We present a new 15 second protocol to characterize hERG (Kv11.1) kinetics, suitable for both manual and high-throughput systems. We demonstrate its use on the Nanion SyncroPatch 384PE, a 384-well automated patch-clamp platform, by applying it to Chinese hamster ovary cells stably expressing hERG1a. From these recordings, we construct 124 cell-specific variants/parameterizations of a hERG model at 25°C. A further eight independent protocols are run in each cell and are used to validate the model predictions. We then combine the experimental recordings using a hierarchical Bayesian model, which we use to quantify the uncertainty in the model parameters, and their variability from cell-to-cell; we use this model to suggest reasons for the variability. This study demonstrates a robust method to measure and quantify uncertainty and shows that it is possible and practical to use high-throughput systems to capture full hERG channel kinetics quantitatively and rapidly.
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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.