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. 2018 Dec 4;8:17626. doi: 10.1038/s41598-018-35858-7

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© The Author(s) 2018

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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The cost function (4) with ε = 0.2 evaluated for pairwise perturbations of the maximum conductances of four major currents for simulated single-channel block of each of the currents. In the upper panel, I_Na is blocked by 50%, and in the next panels, I_CaL, I_Kr and I_K1 are similarly blocked by 50%. Like in Fig. 3, clear minimums are observed at the correct blockages in all four cases.