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Growing evidence indicates that STAR favorably reprograms the electrical substrate by speeding conduction and\/or prolonging repolarization via modulation of ion channel expression, although the mechanisms by which single-fraction radiation mediates durable changes in gene expression are incompletely understood. Here, we identify dynamic changes in the cardiomyocyte epigenome and transcriptome after irradiation (IR) in vivo and in vitro, including durably increased expression and chromatin accessibility of\n                    <jats:italic>Scn5a<\/jats:italic>\n                    (encodes the \u03b1 subunit of the sodium channel, Na\n                    <jats:sub>V<\/jats:sub>\n                    1.5), demonstrating a role for epigenetic memory in conduction velocity (CV) increases observed after STAR. Transcriptomic and epigenetic sequencing further identified dynamic changes in gene expression and regulatory regions involved in cellular repolarization, calcium handling, and metabolism after IR. These changes were mirrored by dose-dependent and cell-autonomous changes in repolarization, calcium flux, and mitochondrial respiration, highlighting important cellular processes that may mediate the therapeutic effects of STAR. Overall, we found that cardiomyocytes exposed to a single fraction of high-dose IR exhibited epigenetic reprogramming that mediated broad and dynamic physiologic responses.\n                  <\/jats:p>","DOI":"10.1172\/jci193087","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T17:00:29Z","timestamp":1771347629000},"source":"Crossref","is-referenced-by-count":2,"title":["Cardiac radiotherapy\u2013induced epigenetic memory underlies electrophysiologic and metabolic reprogramming"],"prefix":"10.1172","volume":"136","author":[{"given":"Samuel D.","family":"Jordan","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Cardiovascular Division,"},{"name":"Center for Noninvasive Cardiac Radiotherapy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhua","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, 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