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A web portal for in-silico action potential predictions

INTRODUCTION: Multiple cardiac ion channels are prone to block by pharmaceutical compounds, and this can have large implications for cardiac safety. The effect of a compound on individual ion currents can now be measured in automated patch clamp screening assays. In-silico action potential models ar...

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Detalles Bibliográficos
Autores principales: Williams, Geoff, Mirams, Gary R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593298/
https://www.ncbi.nlm.nih.gov/pubmed/25963830
http://dx.doi.org/10.1016/j.vascn.2015.05.002
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author Williams, Geoff
Mirams, Gary R.
author_facet Williams, Geoff
Mirams, Gary R.
author_sort Williams, Geoff
collection PubMed
description INTRODUCTION: Multiple cardiac ion channels are prone to block by pharmaceutical compounds, and this can have large implications for cardiac safety. The effect of a compound on individual ion currents can now be measured in automated patch clamp screening assays. In-silico action potential models are proposed as one way of predicting the integrated compound effects on whole-cell electrophysiology, to provide an improved indication of pro-arrhythmic risk. METHODS: We have developed open source software to run cardiac electrophysiology simulations to predict the overall effect of compounds that block I(Kr), I(CaL), I(Na), I(Ks), I(K1) and I(to) to varying degrees, using a choice of mathematical electrophysiology models. To enable safety pharmacology teams to run and evaluate these simulations easily, we have also developed an open source web portal interface to this simulator. RESULTS: The web portal can be found at https://chaste.cs.ox.ac.uk/ActionPotential. Users can enter details of compound affinities for ion channels in the form of IC(50) or pIC(50) values, run simulations, store the results for later retrieval, view summary graphs of the results, and export data to a spreadsheet format. DISCUSSION: This web portal provides a simple interface to reference versions of mathematical models, and well-tested state-of-the-art equation solvers. It provides safety teams easy access to the emerging technology of cardiac electrophysiology simulations for use in the drug-discovery process.
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spelling pubmed-45932982015-10-28 A web portal for in-silico action potential predictions Williams, Geoff Mirams, Gary R. J Pharmacol Toxicol Methods Original Article INTRODUCTION: Multiple cardiac ion channels are prone to block by pharmaceutical compounds, and this can have large implications for cardiac safety. The effect of a compound on individual ion currents can now be measured in automated patch clamp screening assays. In-silico action potential models are proposed as one way of predicting the integrated compound effects on whole-cell electrophysiology, to provide an improved indication of pro-arrhythmic risk. METHODS: We have developed open source software to run cardiac electrophysiology simulations to predict the overall effect of compounds that block I(Kr), I(CaL), I(Na), I(Ks), I(K1) and I(to) to varying degrees, using a choice of mathematical electrophysiology models. To enable safety pharmacology teams to run and evaluate these simulations easily, we have also developed an open source web portal interface to this simulator. RESULTS: The web portal can be found at https://chaste.cs.ox.ac.uk/ActionPotential. Users can enter details of compound affinities for ion channels in the form of IC(50) or pIC(50) values, run simulations, store the results for later retrieval, view summary graphs of the results, and export data to a spreadsheet format. DISCUSSION: This web portal provides a simple interface to reference versions of mathematical models, and well-tested state-of-the-art equation solvers. It provides safety teams easy access to the emerging technology of cardiac electrophysiology simulations for use in the drug-discovery process. Elsevier 2015 /pmc/articles/PMC4593298/ /pubmed/25963830 http://dx.doi.org/10.1016/j.vascn.2015.05.002 Text en © 2015 The Authors. Published by Elsevier Inc. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Article
Williams, Geoff
Mirams, Gary R.
A web portal for in-silico action potential predictions
title A web portal for in-silico action potential predictions
title_full A web portal for in-silico action potential predictions
title_fullStr A web portal for in-silico action potential predictions
title_full_unstemmed A web portal for in-silico action potential predictions
title_short A web portal for in-silico action potential predictions
title_sort web portal for in-silico action potential predictions
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593298/
https://www.ncbi.nlm.nih.gov/pubmed/25963830
http://dx.doi.org/10.1016/j.vascn.2015.05.002
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