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The sinoatrial node is perhaps one of the most important tissues in the entire body: it is the natural pacemaker of the heart, making it responsible for initiating each-and-every normal heartbeat. As such, its activity is heavily controlled, allowing heart rate to rapidly adapt to changes in physiological demand. Control of sinoatrial node activity, however, is complex, occurring through the autonomic nervous system and various circulating and locally released factors. In this review we discuss the coupled-clock pacemaker system and how its manipulation by neurohumoral signaling alters heart rate, considering the multitude of canonical and non-canonical agents that are known to modulate sinoatrial node activity. For each, we discuss the principal receptors involved and known intracellular signaling and protein targets, highlighting gaps in our knowledge and understanding from experimental models and human studies that represent areas for future research.
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http://dx.doi.org/10.3389/fphys.2020.00170 | DOI Listing |
PLoS One
September 2025
Department of Cell Physiology, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
Sinoatrial node (SAN) dysfunction often accompanies supraventricular tachyarrhythmias such as atrial fibrillation (AF), which is referred to as tachycardia-bradycardia syndrome (TBS). Although there have been many studies on electrical remodeling in TBS, the regulatory mechanisms that cause electrical remodeling in the SAN and atrial muscles by chronic bradycardia or tachycardia have not yet been fully investigated. Here we hypothesized Pitx2c, a transcription factor that played a central role in the late aspects of left-right asymmetric morphogenesis, regulated an interrelationship between the SAN and the atrial muscles and was involved in TBS-like pathology.
View Article and Find Full Text PDFbioRxiv
August 2025
Department of Physiology & Membrane Biology, School of Medicine, University of California, Davis, USA.
Pacemaker myocytes of the sinoatrial (SA) node initiate each heartbeat through coupled voltage and Ca oscillators, but whether ATP supply is regulated on a beat-by-beat schedule in these cells has been unclear. Using genetically encoded sensors targeted to the cytosol and mitochondria, we tracked beat-resolved ATP dynamics in intact mouse SA node and isolated myocytes. Cytosolic ATP rose transiently with each Ca transient and segregated into high- and low-gain phenotypes defined by the Ca-ATP coupling slope.
View Article and Find Full Text PDFMalays J Pathol
August 2025
International Islamic University Malaysia, Sultan Ahmad Shah Medical Centre, Department of Pathology and Laboratory Medicine (PALM), Forensic Unit, Pahang, Malaysia.
Introduction: Sudden unexpected death (SUD) in a healthy young adult presents a challenging scenario that forensic pathologists often encounter. Although they are rare, thyroid diseases such as hyperthyroidism, hypothyroidism, and lymphocytic thyroiditis can contribute to SUD. Comprehensive investigations, including thyroid histological evaluation, are critical to identify underlying causes.
View Article and Find Full Text PDFFront Med (Lausanne)
August 2025
Centro de Simulación Computacional para Aplicaciones Tecnológicas (CSC-CONICET), Buenos Aires, Argentina.
Introduction: This study focused on the complex structure of heart rate variability (HRV) in the healthy heart. We studied the behavior of the heart rate variability (HRV) in healthy humans as a function of age from conception, including fetal data. We calculated statistical quantities such as the mean value of RR intervals (
Heart Rhythm
August 2025
XXX. Electronic address:
Here we report a novel electroanatomic mapping method to determine intramural activation, which we call electro-tomographic mapping. Based on our previous experiments, which demonstrated that multipolar electrograms can resolve near-field activity with little contamination in the x/y-plane but with a confocal view in the z axis, we designed a strategy for identifying activation from a focal source deep to the mapping surface through a combination of annotating the earliest -dV/dtmax and identification of a multipolar QS signal. We hypothesized that this strategy would be of use to map the true superior "North" sub-epicardial activation of the sinoatrial node (SAN) to facilitate catheter ablation in a challenging case of inappropriate sinus tachycardia.
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