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Reciprocal interaction between IK1 and If in biological pacemakers: A simulation study
Yacong Li1, Kuanquan Wang1, Qince Li1,2
1School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China.
Plos Computational Biology
|March 10, 2021
Summary
Biological pacemakers offer an alternative to electronic devices for treating heart rhythm disorders. This study computationally investigates combining inward rectifier potassium (IK1) and funny current (If) channel modifications to create stable, engineered pacemaker cells from ventricular myocytes.
Area of Science:
- Cardiovascular physiology
- Computational biology
- Biomedical engineering
Background:
- Pacemaking dysfunction (PD) causes heart rhythm disorders, syncope, and death.
- Current electronic pacemakers have limitations like finite battery life and surgical risks.
- Biological pacemakers engineered from ventricular myocytes (VMs) are a potential alternative.
Purpose of the Study:
- To investigate the mechanisms by which regulating inward rectifier potassium (IK1) and funny current (If) channels generates spontaneous pacemaking activity in VMs.
- To determine if simultaneous modification of IK1 and If enhances the stability of bio-engineered pacemaker action potentials.
- To provide theoretical insights for designing robust biological pacemakers.
Main Methods:
- Computational modeling of ventricular myocytes.
- Analysis of IK1 and If channel densities and their interactions.
- Evaluation of parameter spaces for pacemaking action potential generation.
Main Results:
- A reciprocal interaction between IK1 and If was identified in the ventricular pacemaker model.
- IK1 depression had a mono-phasic effect, while If augmentation had a bi-phasic effect on pacemaking.
- Moderate If increase enhanced pacemaking; excessive If increase led to slowed or unstable rates.
Conclusions:
- The interplay between IK1 and If is crucial for generating stable pacemaker cells from non-pacemaking VMs.
- Understanding this interplay offers theoretical insights for developing engineered biological pacemakers.
- This research may aid in designing more effective biological pacemaker applications.
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