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TitleModulation of Cardiac Tissue Electrophysiological Properties with Light-Sensitive Proteins
AuthorUdi Nussinovitch, Rami Shinnawi and Lior Gepstein
Affiliation(s)Correspondence: Lior Gepstein, MD, PhD. Rappaport Faculty of Medicine and Research Institute, Technion – Israel Institute of Technology. POB 9649, Haifa 31096, Israel. Tel.: +972-4-8295303; fax: +972-4-8524758. E-mail: mdlior@tx.technion.ac.il.
Published Cardiovasc Res (2014) doi: 10.1093/cvr/cvu037 First published online: February 11, 2014
Keyword624nm Optogenetics pacing cell and gene therapies cardiac resynchronization therapy conduction block
Snippet... entire culture was used. For activation of ArchT, a high-output 624nm LED illumination system was used (Prizmatix, Israel), which was coupled with a 2mm optical fiber. Continuous (30sec) illuminations were carried out during the MEA recordings. Statistical Analysis ...
AbstractA combined cell and gene therapy strategy was developed in which fibroblasts were transfected to express the light-activated depolarizing channel Channelrhodopsin-2 (ChR2). Patch-clamp studies confirmed the development of a robust inward current in the engineered fibroblasts following monochromatic blue-light exposure. The engineered cells were co-cultured with neonatal rat cardiomyocytes (or human embryonic stem cell-derived cardiomyocytes) and studied using a multielectrode array mapping technique. These studies revealed the ability of the ChR2-fibroblasts to electrically couple and pace the cardiomyocyte cultures at varying frequencies in response to blue-light flashes. Activation mapping pinpointed the source of this electrical activity to the engineered cells. Similarly, diffuse seeding of the ChR2-fibroblasts allowed multisite optogenetics pacing of the co-cultures, significantly shortening their electrical activation time and synchronizing contraction. Next, optogenetics pacing in an in-vitro model of conduction block allowed the resynchronization of the tissue's electrical activity. Finally, the ChR2-fibroblasts were transfected to also express the light-sensitive hyperpolarizing proton-pump Archaerhodopsin-T (Arch-T). Seeding of the ChR2/ArchT-fibroblasts allowed to either optogentically pace the cultures (in response to blue-light flashes) or to completely suppress the cultures' electrical activity (following continuous illumination with 624 nm monochromatic-light, activating ArchT).


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