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. 2020 Nov 3;11:5555. doi: 10.1038/s41467-020-19304-9

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© The Author(s) 2020

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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Fig. 8 — a Telemetric ECG traces from a male HCN4FEA mouse with alternating episodes of sinus rhythm and junctional escape rhythm (JER) rhythm (left) and corresponding RR tachogram (right, top). Inset: During escape rhythm the P wave (red) occurs after the QRS complex. b Number of JER episodes during 3 h in low activity phase (n = 11 HCN4FEA animals). c Optical action potentials (OAP) and surface ECGs recorded from a WT (left) and HCN4FEA (right) Langendorff-perfused heart explanted from female mice. The HCN4FEA heart displays JER. The ventricular signal precedes the atrial signal in beat #3–5. d Activation maps determined from the OAP measurements shown in c. Right, activation maps for beats #1, and 3–5 were similar. Activation map for beat #2: anterograde activation of ventricles and retrograde activation of atria from the junction. e (upper panel) Conduction times determined from d. Numbers indicate atrial (top), atrioventricular (middle), and ventricular (bottom) conduction times in ms. Right, Beat 1: ventricles were activated 10 ms after atrial activation. Beat 3–5: ventricles were activated by a subsidiary pacemaker close to the AV junction before atria activation by the SAN. Beat 2: atrial and ventricular activation occurred simultaneously. e (lower panel) Schematic ladder diagrams were determined from the measurements shown in d, e. f Right heart catheterisation of a Langendorff-heart preparation via the superior vena cava from male WT (left) and HCN4FEA (right) animals. Surface (upper panel) and intracardiac ECGs (lower panel). Right, HCN4FEA Langendorff-perfused heart during JER induced by isoproterenol application. Inset: magnification of ECG traces. A His deflection (H, red) precedes the ventricular and atrial signal indicating that the subsidiary pacemaker is localised proximal to the bundle of His. Boxplots show the median line, perc 25/75, and min/max value; open symbols represent the mean value. Source data are provided as a Source Data file.