{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T19:02:18Z","timestamp":1785178938186,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,23]]},"group-title":"Biophysics","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HD108839"],"award-info":[{"award-number":["R01HD108839"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30HD040677"],"award-info":[{"award-number":["P30HD040677"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL165751"],"award-info":[{"award-number":["R01HL165751"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL169610"],"award-info":[{"award-number":["R01HL169610"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Cardiac electrophysiology adapts throughout pediatric development, driven by factors including age-associated ion channel expression changes and decreasing heart rate. Our prior transcriptomic-guided simulations of human atrial cardiomyocytes predicted developmental-associated changes in electrophysiology biomarkers at a fixed pacing rate, leaving the contribution of age- and patient-specific heart rate unresolved. In this study, we incorporated intrinsic heart rate into gene expression-guided computational models to predict the interaction between developmental maturation and pacing rate to shape atrial electrophysiology. Virtual patient-specific populations of atrial cardiomyocytes were generated from the right atrial cardiomyocyte gene expression data from 117 patients, spanning neonates to young adults. We simulated each population at pacing rates corresponding to each patient\u2019s intrinsic ECG-based heart rate and at fixed rates corresponding to the patient cohort minimum, median, and maximum. Action potential and calcium transient biomarkers were quantified, and partial least squares regression assessed key biomarker dependencies. For intrinsic-rate pacing conditions, action potential duration at 50% and 90% repolarization increased with age, whereas early repolarization shortened; maximum upstroke velocity increased, resting membrane potential became more negative, and alternans prevalence decreased. Developmental differences persisted during fixed-rate pacing conditions, indicating that differences were not explained solely by the faster heart rates of younger patients. Notably, intrinsic-rate simulations exhibited stronger age associations for upstroke velocity and alternans than fixed-rate simulations. Sensitivity analyses indicated that electrophysiological phenotypes arose from interactions among ionic conductances, calcium handling, age, and heart rate. Collectively, we find that pediatric atrial electrophysiology reflects both intrinsic developmental remodeling and rate-dependent modulation.<\/jats:p>","DOI":"10.64898\/2026.07.21.739866","type":"posted-content","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T11:25:27Z","timestamp":1784805927000},"source":"Crossref","is-referenced-by-count":0,"title":["Patient-Specific Heart Rate Modulates Developmental Electrophysiology in Transcriptomic-Guided In Silico Models of Pediatric Human Atrial Cardiomyocytes"],"prefix":"10.64898","author":[{"given":"Gabriella M.","family":"Ellks","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario J.","family":"Mendez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devon","family":"Guerrelli","sequence":"additional","affiliation":[{"name":"Children\u2019s National Heart and Lung Institute, Children\u2019s National Hospital, Washington, DC"},{"name":"Sheikh Zayed Institute for Pediatric Surgical Innovation, Children\u2019s National Hospital, Washington, DC"},{"name":"Department of Biomedical Engineering, The George Washington University, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob A.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manan","family":"Desai","sequence":"additional","affiliation":[{"name":"Children\u2019s National Heart and Lung Institute, Children\u2019s National Hospital, Washington, DC"},{"name":"Division of Cardiovascular Surgery, Children\u2019s National Hospital, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"d\u2019Udekem","sequence":"additional","affiliation":[{"name":"Children\u2019s National Heart and Lung Institute, Children\u2019s National Hospital, Washington, DC"},{"name":"Division of Cardiovascular Surgery, Children\u2019s National Hospital, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikki Gillum","family":"Posnack","sequence":"additional","affiliation":[{"name":"Children\u2019s National Heart and Lung Institute, Children\u2019s National Hospital, Washington, DC"},{"name":"Sheikh Zayed Institute for Pediatric Surgical Innovation, Children\u2019s National Hospital, Washington, DC"},{"name":"Department of Pharmacology and Physiology, The George Washington University, Washington, DC"},{"name":"Department of Pediatrics, The George Washington University, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1170-0419","authenticated-orcid":false,"given":"Seth H.","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, The Ohio State University, Columbus, OH"},{"name":"Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026072711501772000_2026.07.21.739866v1.1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000020593"},{"key":"2026072711501772000_2026.07.21.739866v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2006.02.010"},{"key":"2026072711501772000_2026.07.21.739866v1.3","doi-asserted-by":"publisher","DOI":"10.1186\/s13019-021-01518-7"},{"key":"2026072711501772000_2026.07.21.739866v1.4","unstructured":"Imura H , Caputo M , Parry A , Pawade A , Angelini GD. 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