title: Stimulating cardiac muscle by light: cardiac optogenetics by cell delivery.
abstract: BACKGROUND
  After the recent cloning of light-sensitive ion channels and their expression in mammalian cells, a new field, optogenetics, emerged in neuroscience, allowing for precise perturbations of neural circuits by light. However, functionality of optogenetic tools has not been fully explored outside neuroscience, and a nonviral, nonembryogenesis-based strategy for optogenetics has not been shown before.
  
  
  RESULTS
  We demonstrate the utility of optogenetics to cardiac muscle by a tandem cell unit (TCU) strategy, in which nonexcitable cells carry exogenous light-sensitive ion channels, and, when electrically coupled to cardiomyocytes, produce optically excitable heart tissue. A stable channelrhodopsin2 (ChR2)-expressing cell line was developed, characterized, and used as a cell delivery system. The TCU strategy was validated in vitro in cell pairs with adult canine myocytes (for a wide range of coupling strengths) and in cardiac syncytium with neonatal rat cardiomyocytes. For the first time, we combined optical excitation and optical imaging to capture light-triggered muscle contractions and high-resolution propagation maps of light-triggered electric waves, found to be quantitatively indistinguishable from electrically triggered waves.
  
  
  CONCLUSIONS
  Our results demonstrate feasibility to control excitation and contraction in cardiac muscle by light, using the TCU approach. Optical pacing in this case uses less energy, offers superior spatiotemporal control and remote access and can serve not only as an elegant tool in arrhythmia research but may form the basis for a new generation of light-driven cardiac pacemakers and muscle actuators. The TCU strategy is extendable to (nonviral) stem cell therapy and is directly relevant to in vivo applications.
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794-8181, USA.
authors.forename: Zhiheng
authors.initials: Z
authors.lastname: Jia
authors.forename: Virginijus
authors.initials: V
authors.lastname: Valiunas
authors.forename: Zongju
authors.initials: Z
authors.lastname: Lu
authors.forename: Harold
authors.initials: H
authors.lastname: Bien
authors.forename: Huilin
authors.initials: H
authors.lastname: Liu
authors.forename: Hong-Zhang
authors.initials: HZ
authors.lastname: Wang
authors.forename: Barbara
authors.initials: B
authors.lastname: Rosati
authors.forename: Peter R
authors.initials: PR
authors.lastname: Brink
authors.forename: Ira S
authors.initials: IS
authors.lastname: Cohen
authors.forename: Emilia
authors.initials: E
authors.lastname: Entcheva
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D000075402:Channelrhodopsins; D018920:Coculture Techniques; D004285:Dogs; D004558:Electric Stimulation; D005240:Feasibility Studies; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008027:Light; D009119:Muscle Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
chemical_list: D000075402:Channelrhodopsins; D009419:Nerve Tissue Proteins