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Atypical collective oscillatory activity in cardiac tissue uncovered by optogenetics
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Authors
* = equal authorship
- Alexander S. Teplenin
- Nina N. Kudryashova
- Rupamanjari Majumder
- Antoine A.F. de Vries
- Alexander V. Panfilov
- Daniël A. Pijnappels*
- Tim De Coster*
* = equal authorship
FundingERC consolidator grant 101044831 and NWO Vidi grant 917143 (to DAP)ZonMW Off Road grant 04510012110051 (to TDC)
A few questions to understand our research better:
1. What background information would someone who is completely unfamiliar with your field need to know to understand the findings in your paper?
At rest, your heart roughly sends out an electrical signal every second, which makes millions of heart muscle cells beat together. These cells, called cardiomyocytes, usually stay at a resting voltage and respond predictably when activated. An arrhythmia happens when this coordination breaks down, often starting from a small spot that triggers extra heartbeats. In our study, we created such a spot by locally illuminating heart muscle cells equipped with a light‑activated ion channel. A key idea behind the origin of these extra heartbeat triggers is “bi‑stability,” where the cells collectively can stay either in a quiet state or an active, oscillating state, and can switch between these depending on the timing and number of electrical pulses. This concept is central to our findings.
2. What exact research question did you set out to answer and why?
Can we deliberately control the onset and termination of arrhythmia-like activity in cardiac tissue, and is this governed by collective dynamics rather than individual cell behaviour? We tested whether a monolayer of cardiomyocytes, depolarized by local illumination of embedded light-gated ion channels, could be switched between silence and ectopic firing by adjusting the number and frequency of external pacing pulses. This approach highlights the possibility that arrhythmias may arise from coordinated tissue-level mechanisms, offering a new perspective on heart rhythm disorders.
3. What are the most important findings of your paper?
In in vitro monolayers of neonatal rat ventricular cardiomyocyte expressing the optogenetic tool CheRiff, we demonstrated that pacing an illuminated region at specific frequencies and pulse counts can toggle the tissue between a quiescent state and spontaneous ectopic oscillations. Optogenetic stimulation and reaction‑diffusion modelling in silico revealed that this switch only occurs within a “sweet‑spot” of intermediate (resonant) frequency, i.e. too high or too low frequencies fail to induce oscillations. A simplified three-variable model reproduced these dynamics, showing that he effect does not depend on detailed ion channel properties but instead arises from fundamental features of nonlinear excitable systems.
4. Who might eventually benefit from the findings of your study, and what would need to be done before we could achieve these benefits?
Our findings may be of interest to researchers in cardiology, neuroscience, and nonlinear systems science. The interplay between pacing and spatial heterogeneity in generating bi-stable dynamics provides insight not only into arrhythmias, but also into analogous emergent behaviours in neural circuits and other reaction-diffusion systems such as ecological systems and morphogenic biological networks. To move toward clinical or cross-disciplinary applications, further validation in animal or human adult cardiac tissue will be essential.
Journal info
Article type: Research Article
Impact factor: no longer indexed
ISSN: 2050-084X
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