Cardiomyocyte functional screening: interrogating comparative electrophysiology of high-throughput model cell systems

Area of Science:

• Cardiovascular Research
• Electrophysiology
• Drug Discovery

Background:

• Cardiac arrhythmias are a significant health concern, necessitating novel antiarrhythmic therapies.
• Current antiarrhythmic drugs have limitations, including effectiveness and pro-arrhythmia risks.
• Standardized cardiomyocyte models are crucial for high-throughput antiarrhythmic drug screening.

Purpose of the Study:

• To directly compare the electrophysiological properties of three common cardiac cell cultures.
• To assess the response of these cultures to isoproterenol for antiarrhythmic drug development.
• To provide comparative data for selecting appropriate cardiomyocyte models in electrophysiology.

Main Methods:

• Cultured neonatal rat ventricular myocytes (NRVMs), HL-1 cells, and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) on microelectrode arrays (MEAs).
• Recorded extracellular field potentials and mapped conduction velocity.
• Applied the β-adrenoceptor agonist isoproterenol (1 µM) to assess drug response.

Main Results:

• NRVMs exhibited the greatest field potential amplitude and conduction velocity.
• NRVMs and hiPSC-CMs showed rate-dependent field potential durations and responded to isoproterenol.
• HL-1 cells displayed slower conduction, shorter durations, and no response to isoproterenol.

Conclusions:

• NRVMs and hiPSC-CMs are more suitable than HL-1 cells for MEA-based antiarrhythmic drug screening.
• Comparative electrophysiological data informs the selection of cardiomyocyte models for functional screening.
• This study provides essential insights for advancing in vitro arrhythmogenesis research.