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. 2021 Aug 25;11:17168. doi: 10.1038/s41598-021-96474-6

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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 perhttps://doi.org/10.1007/s10450-021-00334-8mitted 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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Altered calcium handling in Na_V1.5 KO iPSC-CMs monolayers. (A) Representative Ca²⁺ transient traces of control and Na_V1.5 KO iPSC-CMs monolayers. Blue arrows indicate the Ca²⁺ activation delay in Na_V1.5 KO recording. (B) Representative Ca²⁺ activation maps at pacing of 1 Hz. The symbol indicating the position of stimulating electrodes, and □ showing the position of the representative recordings. (C) Bar graphs summarizing the Ca²⁺ propagation velocities (CaPVs), (D) the normalized amplitude. (E,F) the Ca²⁺ transient durations at 50 and 80% of the repolarization phase (TD₅₀ and TD₈₀), (G) the half time to peak, and (H) the time constant of repolarization (Decay tau) measured at stimulation frequencies of 0.5, 1 and 1.5 Hz in control (n = 12–15) and Na_V1.5 KO (n = 6–9). (I) Bar graphs showing the spontaneous Ca²⁺ waves frequencies in control (n = 15) and Na_V1.5 KO (n = 10) iPSC-CM monolayers. A replicate (n) represents a single monolayer of iPSC-CMs on which the optical mapping was performed. Bars indicate SEM. *p < 0.05, **p < 0.001, ***p < 0.001 as determined by unpaired t-test. This figure was made using MICROSOFT POWERPOINT Version 2106 (build 14131.20278 Office, https://docs.microsoft.com/en-us/) and PRISM 8 Version 8.0.2 (263, https://www.graphpad.com/).

Inline graphic — Altered calcium handling in Na_V1.5 KO iPSC-CMs monolayers. (A) Representative Ca²⁺ transient traces of control and Na_V1.5 KO iPSC-CMs monolayers. Blue arrows indicate the Ca²⁺ activation delay in Na_V1.5 KO recording. (B) Representative Ca²⁺ activation maps at pacing of 1 Hz. The symbol indicating the position of stimulating electrodes, and □ showing the position of the representative recordings. (C) Bar graphs summarizing the Ca²⁺ propagation velocities (CaPVs), (D) the normalized amplitude. (E,F) the Ca²⁺ transient durations at 50 and 80% of the repolarization phase (TD₅₀ and TD₈₀), (G) the half time to peak, and (H) the time constant of repolarization (Decay tau) measured at stimulation frequencies of 0.5, 1 and 1.5 Hz in control (n = 12–15) and Na_V1.5 KO (n = 6–9). (I) Bar graphs showing the spontaneous Ca²⁺ waves frequencies in control (n = 15) and Na_V1.5 KO (n = 10) iPSC-CM monolayers. A replicate (n) represents a single monolayer of iPSC-CMs on which the optical mapping was performed. Bars indicate SEM. *p < 0.05, **p < 0.001, ***p < 0.001 as determined by unpaired t-test. This figure was made using MICROSOFT POWERPOINT Version 2106 (build 14131.20278 Office, https://docs.microsoft.com/en-us/) and PRISM 8 Version 8.0.2 (263, https://www.graphpad.com/).