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Role of If Density on Electrical Action Potential of Bio-engineered Cardiac Pacemaker: A Simulation Study

Due to the inevitable drawbacks of the implantable electrical pacemaker, the biological pacemaker was believed to be an alternative therapy for heart failure. Previous experimental studies have shown that biological pacemaker could be produced by genetically manipulating non-pacemaking cardiac cells by suppressing the inward rectifier potassium current (IK1) and expressing the hyperpolarization- activated current (If). However, the role of If in such bio-engineered pacemaker is not clear. In this study, we simulated the action potential of biological pacemaker cells by manipulating If-IK1 parameters (i.e., inhibiting IK1 as well as incorporating If) to analyze possible mechanisms by which different If densities control pacemaking action potentials. Our simulation results showed different pacing mechanism between the bioengineered pacemaking cells with and without If. In addition, it was shown that a greater If density might result in a slower pacing frequency, and excessive of it might produce an early-afterdepolarizations-like action potential due to a sudden release of calcium from sarcoplasmic reticulum into the cytoplasm. This study indicated that when IK1 was significantly suppressed, incorporating If may not enhance the pacing ability of biological pacemaker, but lead to abnormal dynamics of intracellular ionic concentration, increasing risks of dysrhythmia in the heart.