title: A web portal for in-silico action potential predictions.
abstract: BACKGROUND
  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 IKr, ICaL, INa, IKs, IK1 and Ito 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 IC50 or pIC50 values, run simulations, store the results for later retrieval, view summary graphs of the results, and export data to a spreadsheet format.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Computational Biology, Dept. of Computer Science, University of Oxford, Oxford OX1 3QD, UK.
authors.forename: Geoff
authors.initials: G
authors.lastname: Williams
authors.affiliation: Computational Biology, Dept. of Computer Science, University of Oxford, Oxford OX1 3QD, UK. Electronic address: gary.mirams@cs.ox.ac.uk.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Mirams
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D003198:Computer Simulation; D022062:Electrophysiologic Techniques, Cardiac / Q000379:methods*; D006801:Humans; D020407:Internet; D007473:Ion Channels / Q000187:drug effects; D008962:Models, Theoretical; D018408:Patch-Clamp Techniques; D012984:Software
chemical_list: D007473:Ion Channels
keywords: Action potential; Cardiac safety; Compound screening; High-throughput; Mathematical model; Open source