TY - JOUR
T1 - Leak current, even with gigaohm seals, can cause misinterpretation of stem cell-derived cardiomyocyte action potential recordings
AU - Clark, Alexander P
AU - Clerx, Michael
AU - Wei, Siyu
AU - Lei, Chon Lok
AU - de Boer, Teun P
AU - Mirams, Gary R
AU - Christini, David J
AU - Krogh-Madsen, Trine
N1 - Publisher Copyright:
©. We show that compensation of this leak current is difficult due to challenges with obtaining accurate measures of R during an experiment. Using simulation, we show that R measures (i) change during an experiment, invalidating the use of pre-rupture values, and (ii) are polluted by the presence of transmembrane currents at every voltage. Finally, we posit that the background sodium current in baseline iPSC-CM models imitates the effects of seal-leak current and is increased to a level that masks the effects of seal-leak current on iPSC-CMs. Conclusion: Based on these findings, we make recommendations to improve iPSC-CM AP data acquisition, interpretation, and model-building. Taking these recommendations into account will improve our understanding of iPSC-CM physiology and the descriptive ability of models built from such data.
PY - 2023/8/2
Y1 - 2023/8/2
N2 - 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.
AB - 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.
KW - Arrhythmias
KW - Computer simulation
KW - Induced pluripotent stem cells
KW - Ion channels
KW - Patch clamp
UR - http://www.scopus.com/inward/record.url?scp=85168803290&partnerID=8YFLogxK
U2 - 10.1093/europace/euad243
DO - 10.1093/europace/euad243
M3 - Article
C2 - 37552789
SN - 1099-5129
VL - 25
JO - 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
JF - 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
IS - 9
M1 - euad243
ER -