Cardiac organoids offer an exciting new methodology for understanding and modeling cardiac disease states, drug safety, and more. Unlike conventional monolayers, cardiac organoids can better model the three-dimensional environments of intact hearts and induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) can even form atrial and ventricular structures (Volmert et al., 2023; Lewis-Israeli et al., 2021). However, it remains challenging to study action potentials (AP) with cardiac organoids, along with drug induced changes to AP waveform shape. 

A Multi Channel Systems' MEA2100 Mini system was used with the Foresee Biosystems IntraCell to obtain reliable and repeatable measurements of action potentials in human cardiac organoids grown at Michigan State University. Unlike traditional MEA recordings that can only measure field potentials, the IntraCell uses a laser to precisely optoporate cardiomyocytes underneath each electrode. This laser optoporation produces action potentials that are reproducible and that are susceptible to drug effects.  

For instance, cardiac organoids were treated with the classic antiarrhythmic dofetilide which lengthened the action potential duration (APD). This lengthening of APD increased as a function of time, with the initial effects of the drug producing an arrythmia followed by a stabilization period. 

In addition to modeling healthy hearts, human cardiac organoids can be made from iPSC-CMs that come from patients with congenital heart disease. These cells produce organoids that are naturally more arrhythmic and compounds can be tested that might restore normal function. Pro-arrhythmic cardiac organoids were treated with quinidine, which stopped the arrhythmic behavior and produced stable consistent beating over a 6-minute period.

Together, these data demonstrate that the MEA2100 Mini and the IntraCell system are a powerful new tool for studying action potentials and drug effects in cardiac organoids. 

Resources:

Lewis-Israeli, Y.R., Wasserman, A.H., Gabalski, M.A. et al. Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease. Nat Commun 12, 5142 (2021). https://doi.org/10.1038/s41467-021-25329-5

Volmert, B., Kiselev, A., Juhong, A. et al. A patterned human primitive heart organoid model generated by pluripotent stem cell self-organization. Nat Commun 14, 8245 (2023). https://doi.org/10.1038/s41467-023-43999-1