{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T01:08:31Z","timestamp":1784768911037,"version":"3.55.0"},"reference-count":60,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>The main challenge in cardiac optogenetics is to have low\u2010power, high\u2010fidelity deep excitation of cells with minimal invasiveness and heating. We present a detailed computational study of optogenetic excitation of human ventricular cardiomyocytes (HVCMs) with new ChRmine, bReaChES and CsChrimson red\u2010shifted opsins to overcome the challenge. Action potentials (APs) in ChRmine\u2010expressing HVCMs can be triggered at 6\u00a0\u00b5W\u00a0mm<jats:sup>\u22122<\/jats:sup> (10\u00a0ms pulse) and 0.7\u00a0\u00b5W\u00a0mm<jats:sup>\u22122<\/jats:sup> (100\u00a0ms pulse) at 585\u00a0nm, which is two orders of magnitude lower than ChR2(H134R). This enables safe sustained excitation of deeply situated cardiac cells with ChRmine (7.46\u00a0mm) and with bReaChES (6.21\u00a0mm) with the light source at the pericardium surface. Deeper excitation up to 10.2\u00a0mm can be achieved with ChRmine by illuminating at 650\u00a0nm. Photostimulation conditions for minimum charge transfer during APs have been determined, which is important for tissue health under sustained excitation. The AP duration for all the opsins is constant up to 100\u00a0ms pulse width but increases thereafter. Interestingly, the AP frequency increases with irradiance under continuous illumination, but APs are suppressed at higher irradiances. The optimal range of irradiance for each opsin to excite HVCMs has been determined. Under optimal photostimulation conditions, each opsin can precisely excite APs up to 2.5\u00a0Hz, while latency and power of light pulse for each AP in a sequence remain most stable and an order of magnitude lower, respectively, in ChRmine\u2010expressing HVCMs. The study highlights the importance of ChRmine and bReaChES for resynchronization, termination of ventricular tachycardia and designing optogenetic cardiac pacemakers with enhanced battery life.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15268-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>This work is the formulation of accurate theoretical models of optogenetic control of human ventricular cardiomyocytes (HVCMs) expressed with newly discovered opsins (ChRmine, bReaChES and CsChrimson).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Under continuous illumination, action potentials in each opsin\u2010expressing HVCMs can only be evoked in a certain range of irradiances.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Action potentials in ChRmine\u2010expressing HVCMs can be triggered at ultra\u2010low power (6\u00a0\u00b5W\u00a0mm<jats:sup>\u22122<\/jats:sup> at 10\u00a0ms pulse or 0.7\u00a0\u00b5W\u00a0mm<jats:sup>\u22122<\/jats:sup> at 100\u00a0ms pulse at 585\u00a0nm), which is two to three orders of magnitude lower than reported results.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Ongoing action potentials in ChRmine\u2010expressing HVCMs can be suppressed by continuous illumination of 585\u00a0nm light at 2\u00a0\u00b5W\u00a0mm<jats:sup>\u22122<\/jats:sup>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ChRmine enables sustained excitation due to its faster recovery from the desensitized state.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Optogenetic excitation of deeply situated cardiac cells is possible up to \u223c7.46\u00a0and 10.2\u00a0mm with ChRmine on illuminating the outer surface of pericardium at safe irradiance at 585\u00a0nm and 650\u00a0nm, respectively.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The study opens up prospects for designing energy\u2010efficient light\u2010induced pacemakers, resynchronization and termination of ventricular tachycardia.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp283366","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T06:29:30Z","timestamp":1662532170000},"page":"4653-4676","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Ultra\u2010low power deep sustained optogenetic excitation of human 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