Sinoatrial Node Impulses Emerge From Unique Synchronization Processing Solutions of Partially Stochastic Local...

Incessant, spontaneous, heterogeneous local calcium (Ca²⁺) oscillations (LCOs) occur throughout the neuronal-like cytoarchitecture of the sinoatrial node (SAN).

The goal of this study was to define how LCO information processing forms recurrent, rhythmic global SAN impulses.

Novel dynamical systems and network analyses were applied to images of Ca²⁺ signals in mouse SANs ex vivo.

Ca²⁺ dynamics generated by self-organization of LCOs within pacemaker cells throughout the SAN were intermediate between highly periodic and stochastic, and formed regional functional clusters with distinct phases, preserved throughout recordings, indicating weak cluster electrical coupling. Cluster dynamics transitioned between stable and unstable fixed points, never achieving equilibrium. Spatiotemporal integration of information encoded during phase overlap throughout the cluster network formed recurrent global Ca²⁺ impulses. Clusters having high degrees of stochasticity, earliest fixed-point instabilities, earliest and highest instantaneous rates of change, and rotor-like energy transitions aligned with the foot of global Ca²⁺ impulse. Small-world functional connectivity structure indicated that global impulses were formed by balancing efficient local information processing with rapid long-range communication across the network of regional clusters. This small-world information transfer allows global impulses to emerge as recurrent "best solutions" computed during each beat from incessant LCOs.

This novel paradigm for SAN impulse formation provides flexibility and reliability for heartbeat regulation that will enhance understanding of SAN autonomic regulation, arrhythmogenesis, and sick sinus syndrome.