ArticlePLoS computational biology2021
Reciprocal interaction between IK1 and If in biological pacemakers: A simulation study.
Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 9 citations in OpenAlex.
- AAV-mediated long-term TBX18 expression causes cardiac fibrosis and fails to induce pacemaker activity in rodents.The Journal of clinical investigation · 2026Article
- Mechanisms of rectified gap junctional coupling enhancing pacemaking activity of biologically engineered pacemaker cells.NPJ systems biology and applications · 2026Article
- A Comprehensive Review of a Mechanism-Based Ventricular Electrical Storm Management.Journal of clinical medicine · 2025Review
- Understanding PITX2-Dependent Atrial Fibrillation Mechanisms through Computational Models.International journal of molecular sciences · 2021Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
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Abstract
Pacemaking dysfunction (PD) may result in heart rhythm disorders, syncope or even death. Current treatment of PD using implanted electronic pacemakers has some limitations, such as finite battery life and the risk of repeated surgery. As such, the biological pacemaker has been proposed as a potential alternative to the electronic pacemaker for PD treatment. Experimentally and computationally, it has been shown that bio-engineered pacemaker cells can be generated from non-rhythmic ventricular myocytes (VMs) by knocking out genes related to the inward rectifier potassium channel current (IK1) or by overexpressing hyperpolarization-activated cyclic nucleotide gated channel genes responsible for the "funny" current (If). However, it is unclear if a bio-engineered pacemaker based on the modification of IK1- and If-related channels simultaneously would enhance the ability and stability of bio-engineered pacemaking action potentials. In this study, the possible mechanism(s) responsible for VMs to generate spontaneous pacemaking activity by regulating IK1 and If density were investigated by a computational approach. Our results showed that there was a reciprocal interaction between IK1 and If in ventricular pacemaker model. The effect of IK1 depression on generating ventricular pacemaker was mono-phasic while that of If augmentation was bi-phasic. A moderate increase of If promoted pacemaking activity but excessive increase of If resulted in a slowdown in the pacemaking rate and even an unstable pacemaking state. The dedicated interplay between IK1 and If in generating stable pacemaking and dysrhythmias was evaluated. Finally, a theoretical analysis in the IK1/If parameter space for generating pacemaking action potentials in different states was provided. In conclusion, to the best of our knowledge, this study provides a wide theoretical insight into understandings for generating stable and robust pacemaker cells from non-pacemaking VMs by the interplay of IK1 and If, which may be helpful in designing engineered biological pacemakers for application purposes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.