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. 2021 Oct 18;11:20570. doi: 10.1038/s41598-021-99891-9

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© The Author(s) 2021

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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Examples of arrhythmias induced by isoproterenol (Iso) challenge and spontaneous calcium release (SCR) in Lepr^db/db eNOS^−/− (2KO) and high fat diet plus low dose STZ-treated (HFD + STZ) mice. (A) Calcium transients with evidence of spontaneous calcium release (SCR, arrow) following the termination of rapid pacing (S) only in the presence of Iso (top trace). (B) Dual voltage-calcium optical mapping results. Activation maps were determined from action potentials measured simultaneously with calcium transients. The site of arrhythmia initiation (VT first beat, left panel B) is associated with the location of SCR (site a), rather than the absence of SCR (site b) following rapid pacing (s), as depicted in the calcium transient traces (right, Panel B). The activation map corresponding to sinus rhythm is shown in the right panel as a reference. Note the difference in time scale between the two maps.