Dynamic interactions and mutual synchronization of sinoatrial node pacemaker cells. A mathematical model

Area of Science:

• Computational biology
• Cardiac electrophysiology
• Mathematical modeling

Background:

• Sinoatrial node pacemaker cells exhibit dynamic interactions and mutual entrainment.
• Understanding these interactions is crucial for explaining coordinated heart rhythms.

Purpose of the Study:

• To investigate dynamic interactions and mutual entrainment of coupled sinoatrial pacemaker cells with varying intrinsic frequencies.
• To explain the ionic basis of phase-dependent interactions and synchronization mechanisms.

Main Methods:

• Utilized a computerized mathematical model to simulate transmembrane potentials of coupled sinoatrial pacemaker cells.
• Altered intrinsic cell frequencies via hyperpolarizing current or slow inward current adjustments.
• Simulated linear arrays of cells coupled by ohmic resistances.

Main Results:

• Simulations reproduced experimental findings on electrotonic and phase-dependent pacemaker interactions.
• Demonstrated that mutual entrainment leads to synchronization at various harmonic and complex ratios (e.g., 1:1, 2:1, 3:2).
• Observed complex pacemaker activities like 2:1 sinoatrial block and dysrhythmia in larger cell arrays.

Conclusions:

• Synchronization arises from mutual,
• democratic
• interactions among pacemaker cells, rather than a dominant pacemaker influence.
• The model provides insights into the ionic basis of pacemaker interactions and predicts complex cellular behaviors.
• Results can inform predictions of higher-order interactions in the thousands of cells comprising the sinus node.