Heather B. Hayes, Anthony M. Nicolini, Colin A. Arrowood, Stacie A. Chvatal, David W. Wolfson, Hee Cheol Cho, Denise D. Sullivan, Jérome Chal, Bernard Fermini, Mike Clements, James D. Ross, and Daniel C. Millard
Scientific Reports, 15 August 2019
The cardiac action potential (AP) is vital for understanding healthy and diseased cardiac biology and drug safety testing. However, techniques for high throughput cardiac AP measurements have been limited. Here, we introduce a novel technique for reliably increasing the coupling of cardiomyocyte syncytium to planar multiwell microelectrode arrays, resulting in a stable, label-free local extracellular action potential (LEAP™). We characterized the reliability and stability of LEAP™, its relationship to the field potential, and its efficacy for quantifying AP morphology of human induced pluripotent stem cell derived and primary rodent cardiomyocytes. Rise time, action potential duration, beat period, and triangulation were used to quantify compound responses and AP morphology changes induced by genetic modification. LEAP™ is the first high throughput, non-invasive, label-free, stable method to capture AP morphology from an intact cardiomyocyte syncytium. LEAP™ can accelerate our understanding of stem cell models, while improving the automation and accuracy of drug testing.
