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dc.contributor.authorGanji, Elahe
dc.contributor.authorChan, C Savio
dc.contributor.authorWard, Christopher W
dc.contributor.authorKillian, Megan L
dc.date.accessioned2020-12-10T14:58:51Z
dc.date.available2020-12-10T14:58:51Z
dc.date.issued2020-08-10
dc.identifier.urihttp://hdl.handle.net/10713/14236
dc.description.abstractPurpose: Optogenetics is an emerging alternative to traditional electrical stimulation to initiate action potentials in activatable cells both ex vivo and in vivo. Optogenetics has been commonly used in mammalian neurons and more recently, it has been adapted for activation of cardiomyocytes and skeletal muscle. Therefore, the aim of this study was to evaluate the stimulation feasibility and sustain isometric muscle contraction and limit decay for an extended period of time (1s), using non-invasive transdermal light activation of skeletal muscle (triceps surae) in vivo. Materials and Methods: We used inducible Cre recombination to target expression of Channelrhodopsin-2 (ChR2(H134R)-EYFP) in skeletal muscle (Acta1-Cre) in mice. Fluorescent imaging confirmed that ChR2 expression is localized in skeletal muscle and does not have specific expression in sciatic nerve branch, therefore, allowing for non-nerve mediated optical stimulation of skeletal muscle. We induced muscle contraction using transdermal exposure to blue light and selected 10 Hz stimulation after controlled optimization experiments to sustain prolonged muscle contraction. Results: Increasing the stimulation frequency from 10 Hz to 40 Hz increased the muscle contraction decay during prolonged 1s stimulation, highlighting frequency dependency and importance of membrane repolarization for effective light activation. Finally, we showed that optimized pulsed optogenetic stimulation of 10 Hz resulted in comparable ankle torque and contractile functionality to that of electrical stimulation. Conclusions: Our results demonstrate the feasibility and repeatability of non-invasive optogenetic stimulation of muscle in vivo and highlight optogenetic stimulation as a powerful tool for non-invasive in vivo direct activation of skeletal muscle.en_US
dc.description.sponsorshipEunice Kennedy Shriver National Institute of Child Health and Human Development (R03 HD094594 to MLK) and The National Institute of Neurological Disorders and Stroke (R01 NS069777 to CSC).en_US
dc.description.urihttps://doi.org/10.1080/03008207.2020.1798943en_US
dc.language.isoenen_US
dc.publisherTaylor and Francis Inc.en_US
dc.relation.ispartofConnective Tissue Researchen_US
dc.subjectOptogeneticsen_US
dc.subjectchannelrhodopsin-2en_US
dc.subjectcre-loxen_US
dc.subjectskeletal muscleen_US
dc.subjecttriceps suraeen_US
dc.titleOptogenetic activation of muscle contraction .en_US
dc.typeArticleen_US
dc.identifier.doi10.1080/03008207.2020.1798943
dc.identifier.pmid32777957
dc.source.journaltitleConnective tissue research
dc.source.volume62
dc.source.issue1
dc.source.beginpage15
dc.source.endpage23
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryEngland


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