POPDC1 Variants Cause Atrioventricular Node Dysfunction and Arrhythmogenic Changes in Cardiac Electrophysiology and Intracellular Calcium Handling in Zebrafish. 2024

Matthew R Stoyek, and Sarah E Doane, and Shannon E Dallaire, and Zachary D Long, and Jessica M Ramia, and Donovan L Cassidy-Nolan, and Kar-Lai Poon, and Thomas Brand, and T Alexander Quinn
Department of Physiology & Biophysics, Dalhousie University, Halifax, NS B3H 4R2, Canada.

Popeye domain-containing (POPDC) proteins selectively bind cAMP and mediate cellular responses to sympathetic nervous system (SNS) stimulation. The first discovered human genetic variant (POPDC1) is associated with atrioventricular (AV) block, which is exacerbated by increased SNS activity. Zebrafish carrying the homologous mutation (popdc1) display a similar phenotype to humans. To investigate the impact of POPDC1 dysfunction on cardiac electrophysiology and intracellular calcium handling, homozygous popdc1 and popdc1 knock-out (popdc1) zebrafish larvae and adult isolated popdc1 hearts were studied by functional fluorescent analysis. It was found that in popdc1 and popdc1 larvae, heart rate (HR), AV delay, action potential (AP) and calcium transient (CaT) upstroke speed, and AP duration were less than in wild-type larvae, whereas CaT duration was greater. SNS stress by β-adrenergic receptor stimulation with isoproterenol increased HR, lengthened AV delay, slowed AP and CaT upstroke speed, and shortened AP and CaT duration, yet did not result in arrhythmias. In adult popdc1 zebrafish hearts, there was a higher incidence of AV block, slower AP upstroke speed, and longer AP duration compared to wild-type hearts, with no differences in CaT. SNS stress increased AV delay and led to further AV block in popdc1 hearts while decreasing AP and CaT duration. Overall, we have revealed that arrhythmogenic effects of POPDC1 dysfunction on cardiac electrophysiology and intracellular calcium handling in zebrafish are varied, but already present in early development, and that AV node dysfunction may underlie SNS-induced arrhythmogenesis associated with popdc1 mutation in adults.

UI MeSH Term Description Entries
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000075224 Cardiac Conduction System Disease Diseases characterized by pathological irregularities in the HEART CONDUCTION SYSTEM. They may be associated with other heart diseases and syndromes (e.g., BRUGADA SYNDROME; NEUROMUSCULAR DISEASE, HEART BLOCKS), isolated or may result from injuries. You can have a conduction disorder without having an arrhythmia, but some arrhythmias arise from conduction disorders. OMIM: 601144. Cardiac Conduction Defect,Cardiac Conduction Defects,Cardiac Conduction System Diseases,Conduction Defect, Cardiac,Defect, Cardiac Conduction
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001145 Arrhythmias, Cardiac Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction. Arrhythmia,Arrythmia,Cardiac Arrhythmia,Cardiac Arrhythmias,Cardiac Dysrhythmia,Arrhythmia, Cardiac,Dysrhythmia, Cardiac
D001283 Atrioventricular Node A small nodular mass of specialized muscle fibers located in the interatrial septum near the opening of the coronary sinus. It gives rise to the atrioventricular bundle of the conduction system of the heart. AV Node,A-V Node,Atrio-Ventricular Node,A V Node,A-V Nodes,AV Nodes,Atrio Ventricular Node,Atrio-Ventricular Nodes,Atrioventricular Nodes,Node, A-V,Node, AV,Node, Atrio-Ventricular,Node, Atrioventricular,Nodes, A-V,Nodes, AV,Nodes, Atrio-Ventricular,Nodes, Atrioventricular
D015027 Zebrafish An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. Zebrafish is a model organism for drug assay and cancer research. Brachydanio rerio,Danio rerio,B. rerio,D. rerio,Zebra Fish,Zebra Fishes,Zebra danio,Zebrafishes,D. rerios,Fishes, Zebra,Zebra danios,danio, Zebra
D054537 Atrioventricular Block Impaired impulse conduction from HEART ATRIA to HEART VENTRICLES. AV block can mean delayed or completely blocked impulse conduction. AV Block,Atrioventricular Conduction Block,AV Blocks,Atrioventricular Blocks,Atrioventricular Conduction Blocks,Block, AV,Blocks, AV,Conduction Block, Atrioventricular,Conduction Blocks, Atrioventricular
D022062 Electrophysiologic Techniques, Cardiac Methods to induce and measure electrical activities at specific sites in the heart to diagnose and treat problems with the heart's electrical system. Cardiac Electrophysiologic Techniques,Electrophysiologic Study, Cardiac,Atrial Electrogram,Bundle of His Electrogram,Cardiac Electrophysiologic Technics,Cardiac Electrophysiological Techniques,Electrophysiologic Techniques, Intracardiac,Electrophysiological Techniques, Cardiac,Electrophysiological Techniques, Intracardiac,His Bundle Electrogram,Intra-Atrial Electrogram,Intracardiac Electrogram,Intracardiac Electrophysiologic Techniques,Intracardiac Electrophysiological Technics,Intracardiac Electrophysiological Techniques,Programmed Electrostimulation, Cardiac,Transesophageal Electrophysiologic Study,Transesophageal Electrophysiological Study,Atrial Electrograms,Bundle Electrogram, His,Bundle Electrograms, His,Cardiac Electrophysiologic Studies,Cardiac Electrophysiologic Study,Cardiac Electrophysiologic Technic,Cardiac Electrophysiologic Technique,Cardiac Electrophysiological Technique,Cardiac Programmed Electrostimulation,Cardiac Programmed Electrostimulations,Electrogram Bundle, His,Electrogram Bundles, His,Electrogram, Atrial,Electrogram, His Bundle,Electrogram, Intra-Atrial,Electrogram, Intracardiac,Electrograms, Atrial,Electrograms, His Bundle,Electrograms, Intra-Atrial,Electrograms, Intracardiac,Electrophysiologic Studies, Cardiac,Electrophysiologic Studies, Transesophageal,Electrophysiologic Study, Transesophageal,Electrophysiologic Technic, Cardiac,Electrophysiologic Technics, Cardiac,Electrophysiologic Technique, Cardiac,Electrophysiologic Technique, Intracardiac,Electrophysiological Studies, Transesophageal,Electrophysiological Study, Transesophageal,Electrophysiological Technic, Intracardiac,Electrophysiological Technics, Intracardiac,Electrophysiological Technique, Cardiac,Electrophysiological Technique, Intracardiac,Electrostimulation, Cardiac Programmed,Electrostimulations, Cardiac Programmed,His Bundle Electrograms,His Electrogram Bundle,His Electrogram Bundles,Intra Atrial Electrogram,Intra-Atrial Electrograms,Intracardiac Electrograms,Intracardiac Electrophysiologic Technique,Intracardiac Electrophysiological Technic,Intracardiac Electrophysiological Technique,Programmed Electrostimulations, Cardiac,Studies, Cardiac Electrophysiologic,Studies, Transesophageal Electrophysiologic,Studies, Transesophageal Electrophysiological,Study, Cardiac Electrophysiologic,Study, Transesophageal Electrophysiologic,Study, Transesophageal Electrophysiological,Technic, Cardiac Electrophysiologic,Technic, Intracardiac Electrophysiological,Technics, Cardiac Electrophysiologic,Technics, Intracardiac Electrophysiological,Technique, Cardiac Electrophysiologic,Technique, Cardiac Electrophysiological,Technique, Intracardiac Electrophysiologic,Technique, Intracardiac Electrophysiological,Techniques, Cardiac Electrophysiologic,Techniques, Cardiac Electrophysiological,Techniques, Intracardiac Electrophysiologic,Techniques, Intracardiac Electrophysiological,Transesophageal Electrophysiologic Studies,Transesophageal Electrophysiological Studies

Related Publications

Matthew R Stoyek, and Sarah E Doane, and Shannon E Dallaire, and Zachary D Long, and Jessica M Ramia, and Donovan L Cassidy-Nolan, and Kar-Lai Poon, and Thomas Brand, and T Alexander Quinn
February 2020, American journal of physiology. Heart and circulatory physiology,
Matthew R Stoyek, and Sarah E Doane, and Shannon E Dallaire, and Zachary D Long, and Jessica M Ramia, and Donovan L Cassidy-Nolan, and Kar-Lai Poon, and Thomas Brand, and T Alexander Quinn
September 2018, The Journal of physiology,
Matthew R Stoyek, and Sarah E Doane, and Shannon E Dallaire, and Zachary D Long, and Jessica M Ramia, and Donovan L Cassidy-Nolan, and Kar-Lai Poon, and Thomas Brand, and T Alexander Quinn
January 1992, Japanese circulation journal,
Matthew R Stoyek, and Sarah E Doane, and Shannon E Dallaire, and Zachary D Long, and Jessica M Ramia, and Donovan L Cassidy-Nolan, and Kar-Lai Poon, and Thomas Brand, and T Alexander Quinn
February 2001, Croatian medical journal,
Matthew R Stoyek, and Sarah E Doane, and Shannon E Dallaire, and Zachary D Long, and Jessica M Ramia, and Donovan L Cassidy-Nolan, and Kar-Lai Poon, and Thomas Brand, and T Alexander Quinn
January 2009, General physiology and biophysics,
Matthew R Stoyek, and Sarah E Doane, and Shannon E Dallaire, and Zachary D Long, and Jessica M Ramia, and Donovan L Cassidy-Nolan, and Kar-Lai Poon, and Thomas Brand, and T Alexander Quinn
September 2011, Arquivos brasileiros de cardiologia,
Matthew R Stoyek, and Sarah E Doane, and Shannon E Dallaire, and Zachary D Long, and Jessica M Ramia, and Donovan L Cassidy-Nolan, and Kar-Lai Poon, and Thomas Brand, and T Alexander Quinn
March 2024, Chemico-biological interactions,
Matthew R Stoyek, and Sarah E Doane, and Shannon E Dallaire, and Zachary D Long, and Jessica M Ramia, and Donovan L Cassidy-Nolan, and Kar-Lai Poon, and Thomas Brand, and T Alexander Quinn
September 2013, Journal of cellular and molecular medicine,
Matthew R Stoyek, and Sarah E Doane, and Shannon E Dallaire, and Zachary D Long, and Jessica M Ramia, and Donovan L Cassidy-Nolan, and Kar-Lai Poon, and Thomas Brand, and T Alexander Quinn
April 1988, Physiological reviews,
Matthew R Stoyek, and Sarah E Doane, and Shannon E Dallaire, and Zachary D Long, and Jessica M Ramia, and Donovan L Cassidy-Nolan, and Kar-Lai Poon, and Thomas Brand, and T Alexander Quinn
July 2019, Annals of the New York Academy of Sciences,
Copied contents to your clipboard!