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 and in silico modelling, we systematically explored the dynamics of these arrhythmias, which are characterized by local oscillatory activity, by gradually altering the degree of depolarization 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, 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. To further generalize 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.