Human ipsc-derived cardiomyocyte networks on multiwell micro-electrode arrays for recurrent action potential recordings

Viviana Zlochiver, Stacie L. Kroboth, Christopher R. Beal, Jonathan A. Cook, Rosy Joshi-Mukherjee

Research output: Contribution to journalArticle

Abstract

Cardiac safety screening is of paramount importance for drug discovery and therapeutics. Therefore, the development of novel high-throughput electrophysiological approaches for hiPSC-derived cardiomyocyte (hiPSC-CM) preparations is much needed for efficient drug testing. Although multielectrode arrays (MEAs) are frequently employed for field potential measurements of excitable cells, a recent publication by Joshi-Mukherjee and colleagues described and validated its application for recurrent action potential (AP) recordings from the same hiPSC-CM preparation over days. The aim here is to provide detailed step-by-step methods for seeding CMs and for measuring AP waveforms via electroporation with high precision and a temporal resolution of 1 µs. This approach addresses the lack of easy-to-use methodology to gain intracellular access for high-throughput AP measurements for reliable electrophysiological investigations. A detailed work flow and methods for plating of hiPSC-CMs on multiwell MEA plates are discussed emphasizing critical steps wherever relevant. In addition, a custom-built MATLAB script for rapid data handling, extraction and analysis is reported for comprehensive investigation of the waveform analysis to quantify subtle differences in morphology for various AP duration parameters implicated in arrhythmia and cardiotoxicity.

Original languageEnglish (US)
Article numbere59906
JournalJournal of Visualized Experiments
Volume2019
Issue number149
DOIs
StatePublished - Jul 1 2019

Fingerprint

Cardiac Myocytes
Induced Pluripotent Stem Cells
Action Potentials
Electrodes
Throughput
Waveform analysis
Data handling
Plating
MATLAB
Screening
Electroporation
Workflow
Testing
Drug Discovery
Pharmaceutical Preparations
Cardiac Arrhythmias
Safety
Therapeutics

Keywords

  • Action potential
  • Bioengineering
  • Cardiac electrophysiology
  • Drug screening
  • Electroporation
  • Field potential
  • IPSC-derived cardiomyocytes
  • Issue 149
  • Multi-electrode array

ASJC Scopus subject areas

  • Neuroscience(all)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Human ipsc-derived cardiomyocyte networks on multiwell micro-electrode arrays for recurrent action potential recordings. / Zlochiver, Viviana; Kroboth, Stacie L.; Beal, Christopher R.; Cook, Jonathan A.; Joshi-Mukherjee, Rosy.

In: Journal of Visualized Experiments, Vol. 2019, No. 149, e59906, 01.07.2019.

Research output: Contribution to journalArticle

Zlochiver, Viviana ; Kroboth, Stacie L. ; Beal, Christopher R. ; Cook, Jonathan A. ; Joshi-Mukherjee, Rosy. / Human ipsc-derived cardiomyocyte networks on multiwell micro-electrode arrays for recurrent action potential recordings. In: Journal of Visualized Experiments. 2019 ; Vol. 2019, No. 149.
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