Key result
Macroscopic tissue geometry influenced single-cell electrophysiology, causing diverse firing patterns like regular spiking and arrhythmic firing via gap junction-mediated electrical coupling.
Why the study?
Does macroscopic tissue geometry influence the electrical dynamics and firing patterns of individual electrically excitable cells?
Does macroscopic tissue geometry influence the electrical dynamics and firing patterns of individual electrically excitable cells?
Macroscopic tissue geometry significantly influences single-cell electrophysiology and arrhythmia generation in vitro, urging caution when extrapolating in vitro cardiac arrhythmia models to in vivo predictions.
Answers are grounded in this paper and cite their sources.
Urges caution extrapolating in vitro arrhythmia models to in vivo; leaves open tissue geometry effects on clinical electrophysiology.
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 influence electrical dynamics of individual cells. First, we studied an engineered electrically excitable cell line where all voltage-gated channels were well characterized. 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 experimentally 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 present simulation results and scaling arguments which explore how to extrapolate electrophysiological measurements between tissues with different geometries and different gap junction couplings.
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McNamara et al. (2018) studied Arrhythmia. Macroscopic tissue geometry (patterned islands of different shapes) was evaluated on Firing patterns and electrical dynamics. Macroscopic tissue geometry influenced single-cell electrophysiology, causing diverse firing patterns like regular spiking and arrhythmic firing via gap junction-mediated electrical coupling.
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