Document Detail


Modulation of Cardiac Tissue Electrophysiological Properties with Light-Sensitive Proteins.
MedLine Citation:
PMID:  24518144     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIMS: Optogenetics approaches, utilizing light-sensitive proteins, have emerged as unique experimental paradigms to modulate neuronal excitability. We aimed to evaluate whether a similar strategy could be used to control cardiac-tissue excitability.Methods and ResultsA 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).
CONCLUSIONS: The results of this proof-of-concept study highlight the unique potential of optogenetics for future biological pacemaking and resynchronization therapy applications and for the development of novel anti-arrhythmic strategies.
Authors:
Udi Nussinovitch; Rami Shinnawi; Lior Gepstein
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-2-11
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2014 Feb 
Date Detail:
Created Date:  2014-2-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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