Ca/Calmodulin-Dependent Protein Kinase II (CaMKII) Regulates Basal Cardiac Pacemaker Function: Pros and Cons.

The spontaneous firing of the sinoatrial (SA) node, the physiological pacemaker of the heart, is generated within sinoatrial nodal cells (SANCs) and is regulated by a "coupled-clock" pacemaker system, which integrates a "membrane clock", the ensemble of ion channel currents, and an intracellular "Ca clock", sarcoplasmic reticulum-generated local submembrane Ca releases via ryanodine receptors. The interactions within a "coupled-clock" system are modulated by phosphorylation of surface membrane and sarcoplasmic reticulum proteins. Though the essential role of a high basal cAMP level and PKA-dependent phosphorylation for basal spontaneous SANC firing is well recognized, the role of basal CaMKII-dependent phosphorylation remains uncertain.

Structure-Function Relationship of the Ryanodine Receptor Cluster Network in Sinoatrial Node Cells.

The rate of spontaneous action potentials (APs) generated by sinoatrial node cells (SANC) is regulated by local Ca release (LCR) from the sarcoplasmic reticulum via Ca release channels (ryanodine receptors, RyRs). LCR events propagate and self-organize within the network of RyR clusters (Ca release units, CRUs) via Ca-induced-Ca-release (CICR) that depends on CRU sizes and locations: While larger CRUs generate stronger release signals, the network's topology governs signal diffusion and propagation. This study used super-resolution structured illumination microscopy to image the 3D network of CRUs in rabbit SANC.

Lifelong longitudinal assessment of the contribution of multi-fractal fluctuations to heart rate and heart rate variability in aging mice: role of the sinoatrial node and autonomic nervous system.

Aging is a major risk factor for sinoatrial node (SAN) dysfunction, which can impair heart rate (HR) control and heart rate variability (HRV). HR and HRV are determined by intrinsic SAN function and its regulation by the autonomic nervous system (ANS). The purpose of this study was to use multi-scale multi-fractal detrended fluctuation analysis (MSMFDFA; a complexity-based approach to analyze multi-fractal dynamics) to longitudinally assess changes in multi-fractal HRV properties and SAN function in ECG time series recorded repeatedly across the full adult lifespan in mice.