{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T04:22:16Z","timestamp":1793334136474,"version":"4.5.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>\n                      TGF-\u03b2\n                      <jats:sub>1<\/jats:sub>\n                      (transforming growth factor-\u03b2\n                      <jats:sub>1<\/jats:sub>\n                      ) importantly contributes to cardiac fibrosis by controlling differentiation, migration, and collagen secretion of cardiac myofibroblasts. It is still elusive, however, to which extent TGF-\u03b2\n                      <jats:sub>1<\/jats:sub>\n                      alters the electrophysiological phenotype of myofibroblasts and cardiomyocytes and whether it affects proarrhythmic myofibroblast\u2013cardiomyocyte crosstalk observed in vitro.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>\n                      Patch-clamp recordings of cultured neonatal rat ventricular myofibroblasts revealed that TGF-\u03b2\n                      <jats:sub>1<\/jats:sub>\n                      , applied for 24 to 48 hours at clinically relevant concentrations (\u22642.5 ng\/mL), causes substantial membrane depolarization concomitant with a several-fold increase of transmembrane currents. Transcriptome analysis revealed TGF-\u03b2\n                      <jats:sub>1<\/jats:sub>\n                      \u2013dependent changes in 29 of 63 ion channel\/pump\/connexin transcripts, indicating a pleiotropic effect on the electrical phenotype of myofibroblasts. Whereas not affecting cardiomyocyte membrane potentials and cardiomyocyte\u2013cardiomyocyte gap junctional coupling, TGF-\u03b2\n                      <jats:sub>1<\/jats:sub>\n                      depolarized cardiomyocytes coupled to myofibroblasts by \u224820 mV and increased gap junctional coupling between myofibroblasts and cardiomyocytes &gt;5-fold as reflected by elevated connexin 43 and consortin transcripts. TGF-\u03b2\n                      <jats:sub>1<\/jats:sub>\n                      \u2013dependent cardiomyocyte depolarization resulted from electrotonic crosstalk with myofibroblasts as demonstrated by immediate normalization of cardiomyocyte electrophysiology after targeted disruption of coupled myofibroblasts and by cessation of ectopic activity of cardiomyocytes coupled to myofibroblasts during pharmacological gap junctional uncoupling. In cardiac fibrosis models exhibiting slow conduction and ectopic activity, block of TGF-\u03b2\n                      <jats:sub>1<\/jats:sub>\n                      signaling completely abolished both arrhythmogenic conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>\n                      TGF-\u03b2\n                      <jats:sub>1<\/jats:sub>\n                      profoundly alters the electrophysiological phenotype of cardiac myofibroblasts. Apart from possibly contributing to the control of cell function in general, the changes proved to be pivotal for proarrhythmic myofibroblast\u2013cardiomyocyte crosstalk in vitro, which suggests that TGF-\u03b2\n                      <jats:sub>1<\/jats:sub>\n                      may play a potentially important role in arrhythmogenesis of the fibrotic heart.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circep.116.004567","type":"journal-article","created":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T16:48:03Z","timestamp":1495126083000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":74,"title":["TGF-\u03b2\n                    <sub>1<\/sub>\n                    (Transforming Growth Factor-\u03b2\n                    <sub>1<\/sub>\n                    ) Plays a Pivotal Role in Cardiac Myofibroblast Arrhythmogenicity"],"prefix":"10.1161","volume":"10","author":[{"given":"Nicol\u00f2","family":"Salvarani","sequence":"first","affiliation":[{"name":"From the Department of Physiology, University of Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ange","family":"Maguy","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, University of Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano A.","family":"De Simone","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, University of Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Miragoli","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, University of Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Jousset","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, University of Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Rohr","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, University of Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/1755-1536-5-15"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000214537.44195.a3"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.160549"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.110.957647"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/hy0202.103268"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1358\/mf.2003.25.2.723680"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21464"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.206771"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-009-9080-2"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa5619"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01220.2004"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00018.2011"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-002-1000-0"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e3182137e17"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.62.1.65"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(98)77596-4"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.244798"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate\u2014a practical and powerful approach to multiple testing.","volume":"57","author":"Benjamini Y","year":"1995","unstructured":"Benjamini Y, Hochberg Y. 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