title: Simultaneous voltage and calcium mapping of genetically purified human induced pluripotent stem cell-derived cardiac myocyte monolayers.
abstract: BACKGROUND
  Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offer a powerful in vitro tool to investigate disease mechanisms and to perform patient-specific drug screening. To date, electrophysiological analysis of iPSC-CMs has been limited to single-cell recordings or low-resolution microelectrode array mapping of small cardiomyocyte aggregates. New methods of generating and optically mapping impulse propagation of large human iPSC-CM cardiac monolayers are needed.
  
  
  OBJECTIVE
  Our first aim was to develop an imaging platform with versatility for multiparameter electrophysiological mapping of cardiac preparations, including human iPSC-CM monolayers. Our second aim was to create large electrically coupled human iPSC-CM monolayers for simultaneous action potential and calcium wave propagation measurements.
  
  
  RESULTS
  A fluorescence imaging platform based on electronically controlled light-emitting diode illumination, a multiband emission filter, and single camera sensor was developed and utilized to monitor simultaneously action potential and intracellular calcium wave propagation in cardiac preparations. Multiple, large-diameter (≥1 cm), electrically coupled human cardiac monolayers were then generated that propagated action potentials and calcium waves at velocities similar to those commonly observed in rodent cardiac monolayers.
  
  
  CONCLUSIONS
  The multiparametric imaging system presented here offers a scalable enabling technology to measure simultaneously action potential and intracellular calcium wave amplitude and dynamics of cardiac monolayers. The advent of large-scale production of human iPSC-CMs makes it possible to now generate sufficient numbers of uniform cardiac monolayers that can be utilized for the study of arrhythmia mechanisms and offers advantages over commonly used rodent models.
authors.affiliation: Department of Physics, University of Oxford, Oxford, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Lee
authors.forename: Matt
authors.initials: M
authors.lastname: Klos
authors.forename: Christian
authors.initials: C
authors.lastname: Bollensdorff
authors.forename: Luqia
authors.initials: L
authors.lastname: Hou
authors.forename: Paul
authors.initials: P
authors.lastname: Ewart
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kamp
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bizy
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Guerrero-Serna
authors.forename: Peter
authors.initials: P
authors.lastname: Kohl
authors.forename: José
authors.initials: J
authors.lastname: Jalife
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Herron
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D005818:Genetic Engineering / Q000379:methods*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology*