Leak current, even with gigaohm seals, can cause misinterpretation of stem cell-derived cardiomyocyte action potential recordings

Publication date

2023-08-02

Authors

Clark, Alexander P
Clerx, Michael
Wei, Siyu
Lei, Chon Lok
de Boer, Teun PORCID 0000-0002-0561-6491
Mirams, Gary R
Christini, David J
Krogh-Madsen, Trine

Editors

Advisors

Supervisors

Document Type

Article

Collections

Open Access logo

License

cc_by

Abstract

Aims: Human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have become an essential tool to study arrhythmia mechanisms. Much of the foundational work on these cells, as well as the computational models built from the resultant data, has overlooked the contribution of seal-leak current on the immature and heterogeneous phenotype that has come to define these cells. The aim of this study is to understand the effect of seal-leak current on recordings of action potential (AP) morphology. Methods and results: Action potentials were recorded in human iPSC-CMs using patch clamp and simulated using previously published mathematical models.

Keywords

Arrhythmias, Computer simulation, Induced pluripotent stem cells, Ion channels, Patch clamp, Cardiology and Cardiovascular Medicine, Physiology (medical), Journal Article

Citation

Clark, A P, Clerx, M, Wei, S, Lei, C L, de Boer, T P, Mirams, G R, Christini, D J & Krogh-Madsen, T 2023, 'Leak current, even with gigaohm seals, can cause misinterpretation of stem cell-derived cardiomyocyte action potential recordings', Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, vol. 25, no. 9, euad243. https://doi.org/10.1093/europace/euad243