Our results provide new insights for SAN operation that can be helpful to understanding normal SAN function especially at low rates (near criticality) and in HCN4+/Conexin43- cell communities (Bychkov et al., 2020; Fenske et al., 2020), as well as with respect to SAN function in normal aging (linked to deficient cAMP-PKA-Ca signaling (Liu et al., 2014)) and pathological conditions, such as sick sinus syndrome and SAN arrhythmias (Dobrzynski et al., 2007; John and Kumar, 2016). This evidence concerns the gene HCN4 and sick sinus syndrome.