Review
Biochemistry & Molecular Biology
Konstantin Hennis, Martin Biel, Christian Wahl-Schott, Stefanie Fenske
Summary: HCN channels are essential for heart rhythm initiation and regulation, synchronizing pacemaker cells for stable heart function. Entrainment processes in the sinoatrial node play a crucial role in coordinating heart activity and regulating heart rate.
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Colin H. Peters, Pin W. Liu, Stefano Morotti, Stephanie C. Gantz, Eleonora Grandi, Bruce P. Bean, Catherine Proenza
Summary: The study demonstrates that the funny current (If) in sinoatrial node myocytes is persistently active throughout the cardiac cycle, carrying a substantial fraction of both depolarizing and repolarizing net charge movement. Stimulation of beta-adrenergic receptors increases the net depolarizing charge moved by If, suggesting a contribution to the fight-or-flight response in heart rate regulation. Models suggest that the slow rates of activation and deactivation of the HCN4 isoform underlie the persistent activity of If during the sinoatrial action potential.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Physiology
Konstantin Hennis, Martin Biel, Stefanie Fenske, Christian Wahl-Schott
Summary: HCN4 plays a crucial role in regulating heart rate in the sinoatrial node, and the mechanism involved is different from the previously proposed theory.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Eugenio Ricci, Chiara Bartolucci, Stefano Severi
Summary: Since its discovery, the sinoatrial node (SAN) has been a fascinating and complex subject of research, with conflicting evidence and intense debates. Mathematical models of cardiac pacemaking have become increasingly important in understanding phenomena that experimental evaluation cannot reach. This review discusses the most updated SAN computational models and their contribution to our understanding of pacemaking, considering electrophysiological, structural, pathological, and autonomic control aspects.
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Medicinal
Gergo Bitay, Noemi Toth, Szilvia Deri, Jozefina Szlovak, Zsofia Kohajda, Andras Varro, Norbert Nagy
Summary: Sinus pacemaking relies on the interaction between intracellular Ca2+ handling and surface membrane ion channels, with the small-conductance Ca2+-activated K+-channel (I-SK) potentially playing a significant role. This study investigated the role of I-SK in rabbit SAN cells and found that under normal conditions, I-SK has no impact on pacemaking, but it moderately contributes to SAN automaticity under beta-adrenergic activation.
Review
Cardiac & Cardiovascular Systems
Marietta Easterling, Simone Rossi, Anthony J. Mazzella, Michael Bressan
Summary: The cardiac pacemaker cells in the sinoatrial node are essential for initiating the rhythmic contraction of the heart. Understanding the electrical interactions within the sinoatrial node and with the downstream myocardium is critical for defining vulnerabilities in arrhythmic diseases and developing potential cardiac therapeutics.
JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
(2021)
Article
Physiology
Xiangyun Bai, Kuanquan Wang, Mark R. Boyett, Jules C. Hancox, Henggui Zhang
Summary: This study revealed a significant impact of human cardiac hyperpolarization-activated funny current on cardiac rhythm, with a more pronounced effect on pacemaking in the heart. The specific bradycardic agent ivabradine showed differential effects in humans and rabbits at clinical concentrations, emphasizing the importance of species-specific considerations in cardiac modulation.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Stefano Morotti, Haibo Ni, Colin H. Peters, Christian Rickert, Ameneh Asgari-Targhi, Daisuke Sato, Alexey V. Glukhov, Catherine Proenza, Eleonora Grandi
Summary: The study shows that changes in Na+ homeostatic processes dynamically regulate SAN myocyte electrophysiology, with reductions in NKA and NCX function potentially leading to SAN dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Chiara Piantoni, Manuel Paina, David Molla, Sheng Liu, Giorgia Bertoli, Hongmei Jiang, Yanyan Wang, Yi Wang, Yi Wang, Dario DiFrancesco, Andrea Barbuti, Annalisa Bucchi, Mirko Baruscotti
Summary: This study provides a detailed characterization of the effects and mechanism of action of Tongmai Yangxin (TMYX) on pacemaker cells. TMYX slows the spontaneous action potentials rate by reducing the diastolic phase and shifting the I-f activation curve through a reduction of cAMP-induced stimulation of pacemaker channels. TMYX acts by directly antagonizing the cAMP-induced allosteric modulation of the pacemaker channels.
Article
Pharmacology & Pharmacy
Samuel J. Bose, Matthew J. Read, Emily Akerman, Rebecca A. Capel, Thamali Ayagama, Angela Russell, Derek A. Terrar, Manuela Zaccolo, Rebecca A. B. Burton
Summary: Atrial arrhythmias, such as atrial fibrillation, are a major risk for mortality and stroke. This study found that AC1 is involved in the response of atrial tissue and cells to alpha-adrenoceptor stimulation and IP3R calcium release.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Jari M. Tuomi, Loryn J. Bohne, Tristan W. Dorey, Hailey J. Jansen, Yingjie Liu, Douglas L. Jones, Robert A. Rose
Summary: The study showed that ibrutinib and acalabrutinib have distinct effects on atrial electrophysiology and ion channel function. Ibrutinib increased atrial fibrillation susceptibility and impaired sinus node function, while acalabrutinib had no such effects.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Review
Endocrinology & Metabolism
Lina T. Al Kury, Stephanie Chacar, Eman Alefishat, Ali A. Khraibi, Moni Nader
Summary: Diabetes mellitus affects the structure and function of sinoatrial node cells, leading to heart rate variability and cardiomyopathy. The decreased expression of ion transporters and cell-cell communication ports, as well as the abnormal activation of regulatory factors such as RGS4, mitochondrial thioredoxin-2, and CaMKII, contribute to these changes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Tristan W. Dorey, Megan D. Mcrae, Darrell D. Belke, Robert A. Rose
Summary: This study found that hypertensive heart disease in mice results in impaired heart rate responses to sympathetic nervous system activation. This impairment is caused by up-regulation of PDE4D and reduced effects of cAMP on spontaneous action potential firing in sinoatrial node myocytes.
CARDIOVASCULAR RESEARCH
(2023)
Review
Cardiac & Cardiovascular Systems
Claudia Richter, Rabea Hinkel
Summary: Research on diabetic cardiomyopathy relies heavily on animal models, particularly transgenic rodent models. While these models have advantages in terms of genetic traceability and direct measurable effects, they also face challenges in clinical relevance. Other spontaneous diabetes models in larger mammals like dogs and pigs could be more representative for testing translational approaches.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Review
Oncology
Jing Li, Xin Wang, Mudan Ren, Shuixiang He, Yan Zhao
Summary: Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Animal models play a crucial role in studying the pathogenesis and drug development for HCC. This review provides a comprehensive summary of the classification, characteristics, and advances in experimental animal models of HCC, serving as a reference for researchers in model selection.