Local calcium signals in pacemaker cells heart rate and body mass are self-similar from mice to humans

Long-range, power law correlations across species between heart rate (HR) and body mass (BM) have been documented. Heart rate, which varies widely across species, is determined by the frequency and rhythm at which action potentials (APs) are generated by pacemaker cells within the hearts sinoatrial node (SAN). The rate and rhythm of AP firing of SAN pacemaker cells depend upon the kinetics of activation and inactivation of molecular functions operating within a coupled-clock system of chemical (i.e. Ca2+) oscillators and current oscillators that determine the cell membrane potential (Vm). Measuring Ca2+ signals and membrane potential in single pacemaker cells isolated from mouse, guinea-pig, rabbit and human hearts, we uncover novel self-similarity (trans-species power law correlations) between phase shifts kinetics of Ca2+ and Vm domains that occur during AP cycles in single pacemaker cell and (1) AP firing rates in these SAN cells in vitro; (2) heart rate (EKG RR intervals) in vivo; and (3) body mass (BM). These long-range correlations between subcellular events during AP cycles in SAN cells in vitro, and the rate at which heart beats in vivo are manifestation of self-ordered criticality of heart rate regulation across species from mouse to human within a coupled-oscillator system, i.e., phase shifting of activation-inactivation kinetics occurring within and among molecules operating within a coupled-oscillator system. Thus, self-ordered criticality of the pacemaker cells during an AP cycle underlies long-range correlations between HR and BM across these species.