BPS2026 - Sinoatrial node network structure emerges from adaptive gap junction plasticity

The sinoatrial node (SAN) is the primary pacemaker of the heart. Recent studies have shown that the SAN has a complex network structure, composed of heterogeneous cells with varying intrinsic calcium release characteristics and thus oscillatory rates. Further, the connections between cells have been shown to follow a power law pattern, frequently found in emergent systems such as neuronal or social networks. Moreover, the electrical activity within the SAN network is not perfectly synchronized but rather emerges hierarchically from the cellular activity and network structure to generate a coherent impulse. The SAN network structure, with a neuronal-like distribution of connections implies a more complex developmental process compared to working myocardium, which is generally a syncytium where myocytes are simply connected to their nearest neighbors. However, the process by which this structure is created and maintained is not currently well defined. In our previous work, we showed how SAN cells express and maintain an adequate ion channel composition through a minimal calcium-based feedback system. Further, we found that in a simply connected 2D tissue, this leads to the emergence of pacemaker clusters and an intrinsically variable tissue oscillatory rate. Here, we expand on our previous work by modeling SAN activity in an adaptive network, where nodes (i.e., cells) have variable conductances governed by the calcium feedback model, while edges (i.e., cell connections) are plastic. For edge plasticity, we use a neuronal derived spike-timing dependent plasticity model: we assume that any two cells firing together strengthen their connections and thus network edge weights. We find that, starting with a randomly connected initial network, heterogeneous cells self-organize into activity clusters showing a power law distribution in edge weights. These results suggest activity-dependent plasticity may explain the developmental origins of SAN’s complex network topology.