{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T01:07:51Z","timestamp":1779152871867,"version":"3.51.4"},"reference-count":40,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T00:00:00Z","timestamp":1623110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011199","name":"FP7 Ideas: European Research Council","doi-asserted-by":"crossref","award":["IPS CHOP AF,773181"],"award-info":[{"award-number":["IPS CHOP AF,773181"]}],"id":[{"id":"10.13039\/100011199","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"crossref","award":["1088\/18"],"award-info":[{"award-number":["1088\/18"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"crossref","award":["18CVD05"],"award-info":[{"award-number":["18CVD05"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,8]]},"abstract":"<jats:p>Abnormal action potential (AP) properties, as occurs in long or short QT syndromes (LQTS and SQTS, respectively), can cause life-threatening arrhythmias. Optogenetics strategies, utilizing light-sensitive proteins, have emerged as experimental platforms for cardiac pacing, resynchronization, and defibrillation. We tested the hypothesis that similar optogenetic tools can modulate the cardiomyocyte\u2019s AP properties, as a potentially novel antiarrhythmic strategy. Healthy control and LQTS\/SQTS patient\u2013specific human induced pluripotent stem cell\u2013derived cardiomyocytes (hiPSC-CMs) were transduced to express the light-sensitive cationic channel channelrhodopsin-2 (ChR2) or the anionic-selective opsin, ACR2. Detailed patch-clamp, confocal-microscopy, and optical mapping studies evaluated the ability of spatiotemporally defined optogenetic protocols to modulate AP properties and prevent arrhythmogenesis in the hiPSC-CMs cell\/tissue models. Depending on illumination timing, light-induced ChR2 activation induced robust prolongation or mild shortening of AP duration (APD), while ACR2 activation allowed effective APD shortening. Fine-tuning these approaches allowed for the normalization of pathological AP properties and suppression of arrhythmogenicity in the LQTS\/SQTS hiPSC-CM cellular models. We next established a SQTS\u2013hiPSC-CMs\u2013based tissue model of reentrant-arrhythmias using optogenetic cross-field stimulation. An APD-modulating optogenetic protocol was then designed to dynamically prolong APD of the propagating wavefront, completely preventing arrhythmogenesis in this model. This work highlights the potential of optogenetics in studying repolarization abnormalities and in developing novel antiarrhythmic therapies.<\/jats:p>","DOI":"10.1172\/jci.insight.147470","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T10:56:35Z","timestamp":1623754595000},"source":"Crossref","is-referenced-by-count":18,"title":["Optogenetic modulation of cardiac action potential properties may prevent arrhythmogenesis in short and long QT syndromes"],"prefix":"10.1172","volume":"6","author":[{"given":"Amit","family":"Gruber","sequence":"first","affiliation":[{"name":"Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, the Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel, Haifa, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oded","family":"Edri","sequence":"additional","affiliation":[{"name":"Sohnis Research Laboratory for 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