Using in silico modeling (O' Hara-Rudy dynamic model), the effects of an inhibition of various cardiac currents on the action potential of the human endo-, mid- and epi-cardial myocytes have been tested in order to evaluate their putative involvement in cardiac safety pharmacology. For this purpose, the conductance of each cardiac ionic channels was changed in the ORd algorithm by a scaling factor ranked from 1 (no inhibition) to 0 (full inhibition).
From these results, the effects of each cardiac current inhibition were determined on various cardiac markers such as early afterdepolarization (EAD), transmural dispersion of repolarization (TDR), reverse use dependence (RUD), prolongation or shortening of the action potential duration (APD), triangulation, increase or decrease of maximal rate of action potential rise (Vmax)
For each cardiac current, a file was created describing all these results. As member of the site (please sign in), you have a free access to all these files
At the time being, the tested cardiac currents are the following:
ICaL (Ca++ current through the L-type Ca++ channel), IKr (rapid delayed rectifier K+ current), IKs (slow delayed rectifier K+ current), IK1 (inward rectifier K+ current), INa (Fast Na+ current), INaL (Late Na+ current), Ito (transient outward K+ current)
Other results are in progress.....
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=> If you want only an example, please download the file below (INaL as an example)