Skip to main content

Assay Procedures for Compound Testing of hiPSC-Derived Cardiomyocytes Using Multiwell Microelectrode Arrays

Part of the Methods in Molecular Biology book series (MIMB,volume 1994)

Abstract

The cardiac action potential requires a precise timing of activation and inactivation of ion channel subtypes. Deviations, for example, due to blockage of specific voltage-gated potassium channels, can result in live-threatening arrhythmias. Due to the limitations of standard cellular assays based on cells which artificially express only single ion channel subtypes, many potentially interesting compounds are discarded during drug development. More predictive functional assays are required. With the upcoming of human stem-cell derived cardiomyocytes (hiPS-CM) these assays are available, supporting even the design of patient-derived disease models. Microelectrode array systems allow to noninvasively record and evaluate cardiac field action potentials. In this chapter we describe how to cultivate hiPS-CM on two parallelized MEA systems and suggest an experimental strategy for compound tests.

Key words

  • Microelectrode array
  • MEA
  • Human stem cell-derived cardiomyocytes
  • hiPS
  • Compound testing
  • Safety pharmacology

This is a preview of subscription content, access via your institution.

Buying options

Protocol
USD   49.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-1-4939-9477-9_18
  • Chapter length: 12 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   109.00
Price excludes VAT (USA)
  • ISBN: 978-1-4939-9477-9
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   139.99
Price excludes VAT (USA)
Hardcover Book
USD   199.99
Price excludes VAT (USA)
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Gintant GA, Su Z, Martin RL, Cox BF (2006) Utility of hERG assays as surrogate markers of delayed cardiac repolarization and QT safety. Toxicol Pathol 34:81–90. https://doi.org/10.1080/01926230500431376

    CAS  CrossRef  PubMed  Google Scholar 

  2. Antzelevitch C (2007) Ionic, molecular, and cellular bases of QT-interval prolongation and torsade de pointes. Europace 9(Suppl 4):iv4–i15. https://doi.org/10.1093/europace/eum166

    CrossRef  PubMed  Google Scholar 

  3. Mitcheson JS, Chen J, Lin M et al (2000) A structural basis for drug-induced long QT syndrome. Proc Natl Acad Sci U S A 97:12329

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  4. Morissette P, Hreiche R, Turgeon J (2005) Drug-induced long QT syndrome and torsade de pointes. Can J Cardiol 21:857–864

    CAS  PubMed  Google Scholar 

  5. Stett A, Egert U, Guenther E et al (2003) Biological application of microelectrode arrays in drug discovery and basic research. Anal Bioanal Chem 377:486–495. https://doi.org/10.1007/s00216-003-2149-x

    CAS  CrossRef  PubMed  Google Scholar 

  6. Kraushaar U, Buckenmaier S, Guenther E (2009) MEA-based biosensors to study cellular differentiation and integration. Tissue Eng Part A 15:726–726

    Google Scholar 

  7. Kraushaar U, Meyer T, Hess D et al (2011) Cardiac safety pharmacology: from human ether-a-gogo related gene channel block towards induced pluripotent stem cell based disease models. Expert Opin Drug Saf:1–14. https://doi.org/10.1517/14740338.2012.639358

    CrossRef  PubMed  Google Scholar 

  8. Halbach M, Egert U, Hescheler J, Banach K (2003) Estimation of action potential changes from field potential recordings in multicellular mouse cardiac myocyte cultures. Cell Physiol Biochem 13:271–284. https://doi.org/10.1159/000074542

    CAS  CrossRef  PubMed  Google Scholar 

  9. Millard D, Dang Q, Shi H et al (2018) Cross-site reliability of human induced pluripotent stem cell derived cardiomyocyte based safety assays using microelectrode arrays: results from a blinded CiPA pilot study. Toxicol Sci 164(2):550–562. https://doi.org/10.1093/toxsci/kfy110

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  10. Mulder P, de Korte T, Dragicevic E et al (2018) Predicting cardiac safety using human induced pluripotent stem cell-derived cardiomyocytes combined with multi-electrode array (MEA) technology: a conference report. J Pharmacol Toxicol Methods 91:36–42. https://doi.org/10.1016/j.vascn.2018.01.003

    CAS  CrossRef  PubMed  Google Scholar 

  11. Nyquest H (1928) Certain topics in telegraph transmission theory. Transact Am Inst Electr Eng 47:617–644

    CrossRef  Google Scholar 

  12. Holt GR, Koch C (1999) Electrical interactions via the extracellular potential near cell bodies. J Comput Neurosci 6:169–184. https://doi.org/10.1023/A:1008832702585

    CAS  CrossRef  PubMed  Google Scholar 

  13. Buzsáki G, Anastassiou CA, Koch C (2012) The origin of extracellular fields and currents—EEG, ECoG, LFP and spikes. Nat Rev Neurosci 13:407–420. https://doi.org/10.1038/nrn3241

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  14. Bowlby MR, Peri R, Zhang H, Dunlop J (2008) hERG (KCNH2 or Kv11.1) K+ channels: screening for cardiac arrhythmia risk. Curr Drug Metab 9:965–970

    CAS  CrossRef  PubMed  Google Scholar 

  15. Joshi A, Dimino T, Vohra Y et al (2004) Preclinical strategies to assess QT liability and torsadogenic potential of new drugs: the role of experimental models. J Electrocardiol 37(Suppl):7–14

    CrossRef  PubMed  Google Scholar 

Download references

Acknowledgments

The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under (grant no. 115439), resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies. This publication reflects only the author’s views, and neither the IMI JU nor EFPIA nor the European Commission is liable for any use that may be made of the information contained therein.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Udo Kraushaar .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Verify currency and authenticity via CrossMark

Cite this protocol

Kraushaar, U., Guenther, E. (2019). Assay Procedures for Compound Testing of hiPSC-Derived Cardiomyocytes Using Multiwell Microelectrode Arrays. In: Mandenius, CF., Ross, J. (eds) Cell-Based Assays Using iPSCs for Drug Development and Testing. Methods in Molecular Biology, vol 1994. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9477-9_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-9477-9_18

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9476-2

  • Online ISBN: 978-1-4939-9477-9

  • eBook Packages: Springer Protocols