title: Sensing Cardiac Electrical Activity With a Cardiac Myocyte--Targeted Optogenetic Voltage Indicator.
abstract: BACKGROUND
  Monitoring and controlling cardiac myocyte activity with optogenetic tools offer exciting possibilities for fundamental and translational cardiovascular research. Genetically encoded voltage indicators may be particularly attractive for minimal invasive and repeated assessments of cardiac excitation from the cellular to the whole heart level.
  
  
  OBJECTIVE
  To test the hypothesis that cardiac myocyte-targeted voltage-sensitive fluorescence protein 2.3 (VSFP2.3) can be exploited as optogenetic tool for the monitoring of electric activity in isolated cardiac myocytes and the whole heart as well as function and maturity in induced pluripotent stem cell-derived cardiac myocytes.
  
  
  RESULTS
  We first generated mice with cardiac myocyte-restricted expression of VSFP2.3 and demonstrated distinct localization of VSFP2.3 at the t-tubulus/junctional sarcoplasmic reticulum microdomain without any signs for associated pathologies (assessed by echocardiography, RNA-sequencing, and patch clamping). Optically recorded VSFP2.3 signals correlated well with membrane voltage measured simultaneously by patch clamping. The use of VSFP2.3 for human action potential recordings was confirmed by simulation of immature and mature action potentials in murine VSFP2.3 cardiac myocytes. Optical cardiograms could be monitored in whole hearts ex vivo and minimally invasively in vivo via fiber optics at physiological heart rate (10 Hz) and under pacing-induced arrhythmia. Finally, we reprogrammed tail-tip fibroblasts from transgenic mice and used the VSFP2.3 sensor for benchmarking functional and structural maturation in induced pluripotent stem cell-derived cardiac myocytes.
  
  
  CONCLUSIONS
  We introduce a novel transgenic voltage-sensor model as a new method in cardiovascular research and provide proof of concept for its use in optogenetic sensing of physiological and pathological excitation in mature and immature cardiac myocytes in vitro and in vivo.
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Chang Liao
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Teun P
authors.initials: TP
authors.lastname: de Boer
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mutoh
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Nour
authors.initials: N
authors.lastname: Raad
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Claudia
authors.initials: C
authors.lastname: Richter
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Eva
authors.initials: E
authors.lastname: Wagner
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Downie
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Bernhard
authors.initials: B
authors.lastname: Unsöld
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Iqra
authors.initials: I
authors.lastname: Arooj
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Katrin
authors.initials: K
authors.lastname: Streckfuss-Bömeke
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Stephan
authors.initials: S
authors.lastname: Döker
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Stefan
authors.initials: S
authors.lastname: Luther
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Kaomei
authors.initials: K
authors.lastname: Guan
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagner
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Stephan E
authors.initials: SE
authors.lastname: Lehnart
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Lars S
authors.initials: LS
authors.lastname: Maier
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Walter
authors.initials: W
authors.lastname: Stühmer
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Erich
authors.initials: E
authors.lastname: Wettwer
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Toon
authors.initials: T
authors.lastname: van Veen
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Michael M
authors.initials: MM
authors.lastname: Morlock
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Knöpfel
authors.affiliation: From the Institute of Pharmacology (M.-L.C.L., S.D., E. Wettwer, W.-H.Z.), Clinic for Cardiology and Pulmonology (N.R., E. Wagner, B.U., K.S.-B., K.G., S.W., S.E.L., L.S.M.), and Microarray and Deep-Sequencing Facility (B.R.D.), University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany (M.-L.C.L., N.R., E. Wagner, K.S.-B., S.L., K.G., S.E.L., W.S., W.-H.Z.); Institute of Biomechanics, Technical University Hamburg-Harburg, Hamburg, Germany (M.-L.C.L., M.M.M.); Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands (T.P.d.B., I.A., T.v.V.); Laboratory of Neuronal Circuit Dynamics, RIKEN Brain Science Institute, Saitama, Japan (H.M., T.K.); Max-Planck-Institutes for Dynamics and Self Organization (N.R., C.R., S.L.) and Experimental Medicine (W.S.), Göttingen, Germany; Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany (B.U., S.W., L.S.M.); Department of Medicine and Centre for Neurotechnology, Imperial College London, United Kingdom (T.K.). w.zimmermann@med.uni-goettingen.de.
authors.forename: Wolfram-Hubertus
authors.initials: WH
authors.lastname: Zimmermann
mesh_terms: D000818:Animals; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000502:physiology*; D062308:Optogenetics / Q000379:methods*; D056969:Voltage-Sensitive Dye Imaging / Q000379:methods
keywords: arrhythmias, cardiac; electrophysiology; heart; myocytes, cardiac; optical imaging; optogenetics; stem cells