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. 2017 Nov 21;7:15922. doi: 10.1038/s41598-017-16218-3

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Computational Modeling of I_Ks and I_Kr Block with β-AR Stimulation. Protocol C was repeated in a computational model. The top panel displays AP traces obtained by sequential application of various pharmacologic interventions in the model. Baseline experimental AP traces were accurately reproduced by the model. β-AR stimulation was produced by an increased phosphorylation of all ion channels. The Model was also able to reproduce experimental data for I_Ks block at 80% current blockade. However, I_Kr blockade could not be reproduced using the modified O’Hara-Rudy model. When I_Kr block exceeded 20% early afterdepolarizations (EAD) were observed. EADs were not observed in any preparation even after saturated I_Kr block.