Wave propagation enhances extracellular signal strength in small excitable tissues

Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer new opportunities to study cardiac dynamics and drug responses. High-throughput platforms often rely on extracellular potential (EP) recordings as a proxy for transmembrane voltage, making EP signal strength critical for analysis. EPs arise from spatial inhomogeneities - either intrinsic or induced by wave propagation. Using a computational model, we show that uniform simultaneous stimulation of all cells suppresses wave propagation and results in weak signals. In contrast, localized stimulation that initiates a traveling wave generates much stronger EPs, improving the robustness of biomarker extraction from extracellular recordings.