Improvement of acquisition and analysis methods in multi-electrode array experiments with iPS cell-derived...

Area of Science:

• Cardiovascular Pharmacology
• Stem Cell Biology
• Electrophysiology

Background:

• Multi-electrode array (MEA) systems and human induced pluripotent stem (iPS) cell-derived cardiomyocytes are vital tools for predicting drug-induced QT prolongation and proarrhythmic potential.
• Optimal experimental conditions, including high-pass filter (HPF) frequency and cell plating density, are not yet fully established for reliable electrophysiological characterization.

Purpose of the Study:

• To determine the optimal experimental conditions for MEA recordings of iPS cell-derived cardiomyocytes.
• To investigate the impact of HPF frequency and cell density on the accuracy of electrophysiological measurements.

Main Methods:

• Extracellular field potentials (FPs) were recorded from iPS cell-derived cardiomyocyte sheets using MED64 and MEA2100 systems.
• The effects of 0.1 Hz vs. 1 Hz HPF on FP duration (FPD) were evaluated with and without drug treatment (moxifloxacin, terfenadine, aspirin).
• Cell density influence on FP characteristics and the relationship between FP and action potential (AP) were examined.

Main Results:

• A 0.1-Hz HPF yielded more reliable FP waveforms compared to a 1-Hz HPF, which often resulted in deformed signals.
• The 0.1-Hz HPF allowed for steady-state concentration-response curves for terfenadine-induced FPD changes.
• Increased cell plating density correlated with higher FP waveform peak amplitudes, and FP features corresponded to specific AP repolarization stages and triggered activity.

Conclusions:

• Field potentials recorded from iPS cell-derived cardiomyocytes can effectively assess drug-induced QT prolongation and proarrhythmic potential.
• Careful selection of experimental parameters, particularly HPF frequency, is essential for obtaining robust and reproducible electrophysiological data.