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, that is 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 and in silico modelling, we systematically explored the dynamics of these arrhythmias, which are characterised by local oscillatory activity, by gradually altering the degree of depolarisation in a predefined region. Our findings reveal a bi-stable system, in which transitions between oscillatory ectopic activity and a quiescent state can be precisely controlled, that is by adjusting the number and frequency of propagating waves through the depolarised 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. To further generalise these findings, we demonstrated similar frequency selectivity and bi-stability in a simplified reaction-diffusion model. This suggests that complex ionic cell dynamics are not required to reproduce these effects; rather, simpler non-linear systems can replicate similar behaviour, potentially extending beyond the cardiac context.