Cell Systems
Volume 7, Issue 4, 24 October 2018, Pages 359-370.e6
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Article
Geometry-Dependent Arrhythmias in Electrically Excitable Tissues

https://doi.org/10.1016/j.cels.2018.08.013Get rights and content
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Highlights

  • An engineered excitable cell line becomes arrhythmic when rapidly paced

  • The transition to arrhythmia depends on the geometry of the culture

  • Numerical Hodgkin-Huxley models reproduce these effects

  • Human stem cell-derived cardiomyocytes also show geometry-dependent arrhythmias

Summary

Little is known about how individual cells sense the macroscopic geometry of their tissue environment. Here, we explore whether long-range electrical signaling can convey information on tissue geometry to individual cells. First, we studied an engineered electrically excitable cell line. Cells grown in patterned islands of different shapes showed remarkably diverse firing patterns under otherwise identical conditions, including regular spiking, period-doubling alternans, and arrhythmic firing. A Hodgkin-Huxley numerical model quantitatively reproduced these effects, showing how the macroscopic geometry affected the single-cell electrophysiology via the influence of gap junction-mediated electrical coupling. Qualitatively similar geometry-dependent dynamics were observed in human induced pluripotent stem cell (iPSC)-derived cardiomyocytes. The cardiac results urge caution in translating observations of arrhythmia in vitro to predictions in vivo, where the tissue geometry is very different. We study how to extrapolate electrophysiological measurements between tissues with different geometries and different gap junction couplings.

Keywords

excitable media
electrophysiology
arrhythmia
synthetic biology
dynamical systems

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