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A web portal for in-silico action potential predictions.

Williams G, Mirams GR - J Pharmacol Toxicol Methods (2015)

Bottom Line: 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.It provides safety teams easy access to the emerging technology of cardiac electrophysiology simulations for use in the drug-discovery process.

View Article: PubMed Central - PubMed

Affiliation: Computational Biology, Dept. of Computer Science, University of Oxford, Oxford OX1 3QD, UK.

No MeSH data available.


Inputs and outputs of the action potential simulations. Left: ion current concentration–effect curves are taken from each high throughput screen (HTS) and used to calculate a degree of block at any given concentration. The percentage block is applied to each current in a mathematical model ventricular electrophysiology. We then simulate steady pacing (up to a given time limit), and calculate the action potential and examine its duration. The process is repeated for a range of concentrations, and the results are plotted in a summary graph.
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f0010: Inputs and outputs of the action potential simulations. Left: ion current concentration–effect curves are taken from each high throughput screen (HTS) and used to calculate a degree of block at any given concentration. The percentage block is applied to each current in a mathematical model ventricular electrophysiology. We then simulate steady pacing (up to a given time limit), and calculate the action potential and examine its duration. The process is repeated for a range of concentrations, and the results are plotted in a summary graph.

Mentions: AP-predict uses simple concentration–response curves to determine the degree of reduction to be applied to each channel's maximal conductance, for any given concentration. The simulations integrate the concentration–effect curves from multiple ion channel screens (for any channel listed in Table 1), to predict the effect on the whole cell level, as shown in Fig. 2.


A web portal for in-silico action potential predictions.

Williams G, Mirams GR - J Pharmacol Toxicol Methods (2015)

Inputs and outputs of the action potential simulations. Left: ion current concentration–effect curves are taken from each high throughput screen (HTS) and used to calculate a degree of block at any given concentration. The percentage block is applied to each current in a mathematical model ventricular electrophysiology. We then simulate steady pacing (up to a given time limit), and calculate the action potential and examine its duration. The process is repeated for a range of concentrations, and the results are plotted in a summary graph.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4593298&req=5

f0010: Inputs and outputs of the action potential simulations. Left: ion current concentration–effect curves are taken from each high throughput screen (HTS) and used to calculate a degree of block at any given concentration. The percentage block is applied to each current in a mathematical model ventricular electrophysiology. We then simulate steady pacing (up to a given time limit), and calculate the action potential and examine its duration. The process is repeated for a range of concentrations, and the results are plotted in a summary graph.
Mentions: AP-predict uses simple concentration–response curves to determine the degree of reduction to be applied to each channel's maximal conductance, for any given concentration. The simulations integrate the concentration–effect curves from multiple ion channel screens (for any channel listed in Table 1), to predict the effect on the whole cell level, as shown in Fig. 2.

Bottom Line: 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.It provides safety teams easy access to the emerging technology of cardiac electrophysiology simulations for use in the drug-discovery process.

View Article: PubMed Central - PubMed

Affiliation: Computational Biology, Dept. of Computer Science, University of Oxford, Oxford OX1 3QD, UK.

No MeSH data available.