{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T23:53:31Z","timestamp":1780098811148,"version":"3.54.0"},"reference-count":78,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["HL164453"],"award-info":[{"award-number":["HL164453"]}]},{"name":"National Institute of Health","award":["HL155762"],"award-info":[{"award-number":["HL155762"]}]},{"name":"National Institute of Health","award":["HL132871"],"award-info":[{"award-number":["HL132871"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Patients with ulcerative colitis exhibit an increased risk for supraventricular arrhythmia during the active disease phase of the disease and show signs of atrial electrophysiological remodeling in remission. The goal of this study was to determine the basis for colitis-induced changes in atrial excitability. In a mouse model (C57BL\/6; 3 months) of dextran sulfate sodium (DSS)-induced active colitis (3.5% weight\/volume, 7 days), electrocardiograms (ECG) revealed altered atrial electrophysiological properties with a prolonged P-wave duration and PR interval. ECG changes coincided with a decreased atrial conduction velocity in Langendorff perfused hearts. Action potentials (AP) recorded from isolated atrial myocytes displayed an attenuated maximal upstroke velocity and amplitude during active colitis, as well as a prolonged AP duration (APD). Voltage clamp analysis revealed a colitis-induced shift in the voltage-dependent activation of the Na-current (INa) to more depolarizing voltages. In addition, protein levels of Nav1.5 protein and connexin isoform Cx43 were reduced. APD prolongation depended on a reduction in the transient outward K-current (Ito) mostly generated by Kv4.2 channels. The changes in ECG, atrial conductance, and APD were reversible upon remission. The change in conduction velocity predominantly depended on the reversibility of the reduced Cx43 and Nav1.5 expression. Treatment of mice with inhibitors of Angiotensin-converting enzyme (ACE) or Angiotensin II (AngII) receptor type 1 (AT1R) prevented the colitis-induced atrial electrophysiological remodeling. Our data support a colitis-induced increase in AngII signaling that promotes atrial electrophysiological remodeling and puts colitis patients at an increased risk for atrial arrhythmia.<\/jats:p>","DOI":"10.3390\/biom15070982","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T15:19:31Z","timestamp":1752247171000},"page":"982","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Active Colitis-Induced Atrial Electrophysiological Remodeling"],"prefix":"10.3390","volume":"15","author":[{"given":"Hiroki","family":"Kittaka","sequence":"first","affiliation":[{"name":"Department of Internal Medicine\/Cardiology, Rush University Medical Center, 1750 W. Harrison St., Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J.","family":"Ouille V","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/Cardiology, Rush University Medical Center, 1750 W. Harrison St., Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8653-2283","authenticated-orcid":false,"given":"Carlos H.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/Cardiology, Rush University Medical Center, 1750 W. Harrison St., Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2889-9279","authenticated-orcid":false,"given":"Andr\u00e8s F.","family":"P\u00e9laez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/Cardiology, Rush University Medical Center, 1750 W. Harrison St., Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7969-3369","authenticated-orcid":false,"given":"Ali","family":"Keshavarzian","sequence":"additional","affiliation":[{"name":"Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, 1725 W. Harrison St., Chicago, IL 60612, USA"},{"name":"Department of Internal Medicine\/Gastroenterology, Rush University Medical Center, 1725 W. Harrison St., Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8847-2712","authenticated-orcid":false,"given":"Kathrin","family":"Banach","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/Cardiology, Rush University Medical Center, 1750 W. 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