Atypical collective oscillatory activity in cardiac tissue uncovered by optogenetics

Many biological processes emerge as frequency-dependent responses to trains of external stimuli. Heart rhythm disturbances, i.e., cardiac arrhythmias, are important examples as they are often triggered by specific patterns of preceding stimuli. In this study, we investigated how ectopic arrhythmias can be induced by external stimuli in cardiac tissue containing a localised area of depolarisation. Using optogenetic in vitro experiments, we systematically explored the dynamics of these arrhythmias, which are characterized by local oscillatory activity. Our findings reveal a bi-stable system, in which transitions between oscillatory ectopic activity and a quiescent state can be precisely controlled, i.e., by adjusting the number and frequency of propagating waves through the depolarized area, oscillations could be turned on or off. These frequency-dependent responses arise from collective mechanisms involving stable, non-self-oscillatory cells, contrasting with the typical role of self-oscillations in individual units within biophysical systems.

Methods
Raw optical mapping data were obtained using a mapping setup containing a 100 × 100 pixel CMOS Ultima-L camera (Scimedia, Costa Mesa, CA). The field of view was 16 × 16 mm, resulting in a spatial resolution of 160 μm/pixel. For targeted illumination of monolayers, the setup was optically conjugated to a digitally controlled micro-mirror device (DMD), the Polygon 400 (Mightex Systems, Toronto, ON), with a high-power blue (470 nm) LED (BLS-LCS-0470-50-22-H, Mightex Systems). Electrical stimulation was performed by applying 10-ms-long rectangular electrical pulses with an amplitude of 8 V to a bipolar platinum electrode with a spacing of 1.5 mm between anode and cathode. Data was captured in .rsh and .rsd format.