title: Optical mapping of optogenetically shaped cardiac action potentials.
abstract: Light-mediated silencing and stimulation of cardiac excitability, an important complement to electrical stimulation, promises important discoveries and therapies. To date, cardiac optogenetics has been studied with patch-clamp, multielectrode arrays, video microscopy, and an all-optical system measuring calcium transients. The future lies in achieving simultaneous optical acquisition of excitability signals and optogenetic control, both with high spatio-temporal resolution. Here, we make progress by combining optical mapping of action potentials with concurrent activation of channelrhodopsin-2 (ChR2) or halorhodopsin (eNpHR3.0), via an all-optical system applied to monolayers of neonatal rat ventricular myocytes (NRVM). Additionally, we explore the capability of ChR2 and eNpHR3.0 to shape action-potential waveforms, potentially aiding the study of short/long QT syndromes that result from abnormal changes in action potential duration (APD). These results show the promise of an all-optical system to acquire action potentials with precise temporal optogenetics control, achieving a long-sought flexibility beyond the means of conventional electrical stimulation.
authors.affiliation: Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Park
authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Shin-Rong
authors.initials: SR
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Tung
authors.affiliation: 1] Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA [2] Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA [3] Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD, USA [4] Center for Cell Dynamics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Yue
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D000075402:Channelrhodopsins; D004558:Electric Stimulation; D057809:HEK293 Cells; D025602:Halorhodopsins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008027:Light; D008839:Microelectrodes; D018613:Microscopy, Confocal; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D062308:Optogenetics; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D000075402:Channelrhodopsins; D025602:Halorhodopsins