{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T00:49:18Z","timestamp":1775263758929,"version":"3.50.1"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T00:00:00Z","timestamp":1491350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT098519MA"],"award-info":[{"award-number":["WT098519MA"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"British Heart Foundation (GB)","award":["RE\/08\/004\/23915"],"award-info":[{"award-number":["RE\/08\/004\/23915"]}]},{"name":"British Heart Foundation (GB)","award":["RE\/13\/1\/30181"],"award-info":[{"award-number":["RE\/13\/1\/30181"]}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["3306"],"award-info":[{"award-number":["3306"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["Core-to-Core"],"award-info":[{"award-number":["Core-to-Core"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0174181","type":"journal-article","created":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T14:24:04Z","timestamp":1491402244000},"page":"e0174181","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Non-invasive phenotyping and drug testing in single cardiomyocytes or beta-cells by calcium imaging and optogenetics"],"prefix":"10.1371","volume":"12","author":[{"given":"Yu-Fen","family":"Chang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Connor N.","family":"Broyles","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frances A.","family":"Brook","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cameron W.","family":"Turtle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeharu","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9250-6214","authenticated-orcid":false,"given":"Matthew J.","family":"Daniels","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2017,4,5]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1515\/hsz-2015-0306","article-title":"The impact of recent advances in genetics in understanding disease mechanisms underlying the long QT syndromes","volume":"397","author":"SC Harmer","year":"2016","journal-title":"Biol. Chem"},{"issue":"16","key":"ref2","first-page":"30058","article-title":"The Comprehensive in Vitro Proarrhythmia Assay (CiPA) initiative\u2014Update on progress","author":"T Colatsky","year":"2016","journal-title":"J Pharmacol Toxicol Methods"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.pharmthera.2014.03.004","article-title":"Induced pluripotent stem cell-derived cardiomyocytes for drug development and toxicity testing","volume":"143","author":"D Sinnecker","year":"2014","journal-title":"Pharmacol Ther"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1001\/jama.1922.02640140020008","article-title":"Clinical studies of quinidine. IV. The clinical toxicology of quinidine","volume":"79","author":"RL Levy","year":"1922","journal-title":"J Am Med Assoc"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1016\/j.jacc.2015.12.063","article-title":"Predicting the Unpredictable: Drug-Induced QT Prolongation and Torsades de Pointes","volume":"67","author":"PJ Schwartz","year":"2016","journal-title":"Am Coll Cardiol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1113\/jphysiol.1981.sp013675","article-title":"The effects of heart rate on the action potential of guinea-pig and human ventricular muscle","volume":"313","author":"D. Attwell","year":"1981","journal-title":"J Physiol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.2174\/1875397301206010087","article-title":"A Comparison of the Performance and Application Differences Between Manual and Automated Patch-Clamp Techniques","volume":"6","author":"X Yajuan","year":"2012","journal-title":"Current Chemical Genomics"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1038\/nature08540","article-title":"Electrophysiology in the age of light","volume":"461","author":"M Scanziani","year":"2009","journal-title":"Nature"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/nmeth.1512","article-title":"Optogenetic control of heart muscle in vitro and in vivo","volume":"7","author":"T Bruegmann","year":"2010","journal-title":"Nat. Methods"},{"key":"ref10","first-page":"750","article-title":"Optogenetics for in vivo cardiac pacing and resynchronization therapies","volume":"33","author":"U Nussinovitch","year":"2015"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1093\/cvr\/cvu179","article-title":"Light-induced termination of spiral wave arrhythmias by optogenetic engineering of atrial cardiomyocytes","volume":"104","author":"BO Bingen","year":"2014","journal-title":"Cardiovasc Res"},{"key":"ref12","first-page":"813","article-title":"Optical control of excitation waves in cardiac tissue","volume":"9","author":"RA Burton","year":"2015"},{"key":"ref13","first-page":"16542","article-title":"Cardiac Optogenetics: Enhancement by All-trans-retinal","volume":"5","author":"J Yu","year":"2015"},{"issue":"16","key":"ref14","first-page":"30044","article-title":"Cardiotoxicity screening with simultaneous optogenetic pacing, voltage imaging and calcium imaging","author":"GT Dempsey","year":"2016","journal-title":"J Pharmacol Toxicol Methods"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"11542","DOI":"10.1038\/ncomms11542","article-title":"OptoDyCE as an automated system for high-throughput all-optical dynamic cardiac electrophysiology","volume":"7","author":"A Klimas","year":"2016","journal-title":"Nat Comm"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.stemcr.2014.01.003","article-title":"Rapid cellular phenotyping of human pluripotent stem cell-derived cardiomyocytes using a genetically encoded fluorescent voltage sensor","volume":"2","author":"JS Leyton-Mange","year":"2014","journal-title":"Stem Cell Reports"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.stemcr.2015.08.009","article-title":"Monitoring Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes with Genetically Encoded Calcium and Voltage Fluorescent Reporters","volume":"5","author":"R Shinnawi","year":"2015","journal-title":"Stem Cell Reports"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1038\/nmeth.3000","article-title":"All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins","volume":"8","author":"DR Hochbaum","year":"2014","journal-title":"Nat Methods"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1038\/ncomms2248","article-title":"Luminescent proteins for high-speed single-cell and whole-body imaging","volume":"3","author":"K Saito","year":"2012","journal-title":"Nat Commun"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1021\/cn400012b","article-title":"Improved orange and red Ca<sup>2+<\/sup> indicators and photophysical considerations for optogenetic applications","volume":"4","author":"J Wu","year":"2013","journal-title":"ACS Chem Neurosci"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3389\/fnmol.2013.00002","article-title":"Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics","volume":"6","author":"J Akerboom","year":"2013","journal-title":"Front Mol Neurosci"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1111\/j.1432-0436.2008.00283.x","article-title":"Retinoid acid-induced effects on atrial and pacemaker cell differentiation and expression of cardiac ion channels","volume":"76","author":"N Gassanov","year":"2008","journal-title":"Differentiation"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.stemcr.2014.06.003","article-title":"Calcium transients closely reflect prolonged action potentials in iPSC models of inherited cardiac arrhythmia","volume":"3","author":"CI Spencer","year":"2014","journal-title":"Stem Cell Reports"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"7595","DOI":"10.1073\/pnas.1017210108","article-title":"High efficiency channelrhodopsins for fast neuronal stimulation at low light levels","volume":"108","author":"A Berndt","year":"2011","journal-title":"Proc Natl. Acad. Sci. U.S.A"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1126\/science.1208592","article-title":"An expanded palette of genetically encoded Ca<sup>2+<\/sup> indicators","volume":"333","author":"Y Zhao","year":"2011","journal-title":"Science"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"4760","DOI":"10.1074\/jbc.M110.183780","article-title":"Development of defective and persistent Sendai virus vector: a unique gene delivery\/expression system ideal for cell reprogramming","volume":"286","author":"K Nishimura","year":"2011","journal-title":"J Biol Chem"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"e18556","DOI":"10.1371\/journal.pone.0018556","article-title":"High Cleavage Efficiency of a 2A Peptide Derived from Porcine Teschovirus-1 in Human Cell Lines, Zebrafish and Mice","volume":"6","author":"JH Kim","year":"2011","journal-title":"PLoS ONE"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1161\/CIRCEP.111.964247","article-title":"Stimulating cardiac muscle by light: cardiac optogenetics by cell delivery","volume":"5","author":"Z Jia","year":"2011","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"ref29","article-title":"Human-based approaches to pharmacology and cardiology: an interdisciplinary and intersectorial workshop","author":"B Rodriguez","year":"2015","journal-title":"Europace"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"e40288","DOI":"10.1371\/journal.pone.0040288","article-title":"Maximum Diastolic Potential of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Depends Critically on IKr","volume":"7","author":"MX Doss","year":"2012","journal-title":"PLoS ONE"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bpj.2014.11.008","article-title":"Action Potential Morphology of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Does Not Predict Cardiac Chamber Specificity and Is Dependent on Cell Density","volume":"108","author":"DT Du","year":"2015","journal-title":"Biophys J"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nrcardio.2012.3","article-title":"Potassium-channel mutations and cardiac arrhythmias\u2014diagnosis and therapy","volume":"9","author":"JR Giudicessi","year":"2012","journal-title":"Nat. Rev. Cardiol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.yjmcc.2015.06.021","article-title":"Molecular basis of hERG potassium channel blockade by the class Ic antiarrhythmic flecainide","volume":"86","author":"D Melgari","year":"2015","journal-title":"J Mol Cell Cardiol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nrendo.2013.166","article-title":"K(ATP) channels and islet hormone secretion: new insights and controversies","volume":"9","author":"FM Ashcroft","year":"2013","journal-title":"Nat. Rev. Endo"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/gt.2015.23","article-title":"Optogenetic control of insulin secretion by pancreatic \u03b2-cells in vitro and in vivo","volume":"22","author":"T Kushibiki","year":"2015","journal-title":"Gene Ther"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"e28095","DOI":"10.4161\/isl.28095","article-title":"Optogenetic control of insulin secretion in intact pancreatic islets with \u03b2-cell-specific expression of Channelrhodopsin-2","volume":"6","author":"TM Reinbothe","year":"2014","journal-title":"Islets"},{"key":"ref37","first-page":"467","article-title":"Automated Video-Based Analysis of Contractility and Calcium Flux in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Cultured over Different Spatial Scales","volume":"21","author":"N Huebsch","year":"2015"},{"key":"ref38","doi-asserted-by":"crossref","DOI":"10.1093\/eurheartj\/ehw189","article-title":"Subtype-specific promoter-driven action potential imaging for precise disease modelling and drug testing in hiPSC-derived cardiomyocytes","author":"Z Chen","year":"2016"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"42398","DOI":"10.1038\/srep42398","article-title":"Genetically encoded bioluminescent voltage indicator for multi-purpose use in wide range of bioimaging","volume":"7","author":"S Inagaki","year":"2017","journal-title":"Sci. Rep"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0174181","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T00:14:03Z","timestamp":1540340043000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0174181"}},"subtitle":[],"editor":[{"given":"Johnson","family":"Rajasingh","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2017,4,5]]},"references-count":39,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2017,4,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0174181","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,5]]}}}