Abstract
Inherited arrhythmias and conduction system diseases are known causes of sudden cardiac death and are responsible for significant mortality and morbidity in patients with congenital heart disease and electrical disorders. Knowledge derived from human genetics and studies in animal models have led to the discovery of multiple molecular defects responsible for arrhythmogenesis. This review summarizes the molecular basis of inherited arrhythmias in structurally normal and altered hearts. On the cellular and molecular levels, minor disturbances can provoke severe arrhythmias. Ion channels are responsible for the initiation and propagation of the action potential within the cardiomyocyte. Structural heart diseases, such as hypertrophic or dilated cardiomyopathies, increase the likelihood of cardiac electrical abnormalities. Ion channels can also be upor down-regulated in congenital heart disease, altering action potential cellular properties and therefore triggering arrhythmias. Conduction velocities may be inhomogeneously altered if connexin function, density or distribution changes. Another important group of electrophysiologic diseases is the heterogeneous category of inherited arrhythmias in the structurally normal heart, with a propensity to sudden cardiac death. There have been many recent relevant discoveries that help explain the molecular and functional mechanisms of long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and other electrical myopathies. Identification of molecular pathways allows the identification of new therapeutic targets, for both disease palliation and cure. As more disease-causing mutations are identified and genotypic-phenotypic correlation is defined, families can be screened prior to symptom-onset and patients may potentially be treated in a genotype-specific manner, opening the doors of cardiac electrophysiology to the emerging field of pharmacogenomics.
Current Genomics
Title: Molecular Mechanisms of Inherited Arrhythmias
Volume: 9 Issue: 3
Author(s): Cordula M. Wolf and Charles I. Berul
Affiliation:
Abstract: Inherited arrhythmias and conduction system diseases are known causes of sudden cardiac death and are responsible for significant mortality and morbidity in patients with congenital heart disease and electrical disorders. Knowledge derived from human genetics and studies in animal models have led to the discovery of multiple molecular defects responsible for arrhythmogenesis. This review summarizes the molecular basis of inherited arrhythmias in structurally normal and altered hearts. On the cellular and molecular levels, minor disturbances can provoke severe arrhythmias. Ion channels are responsible for the initiation and propagation of the action potential within the cardiomyocyte. Structural heart diseases, such as hypertrophic or dilated cardiomyopathies, increase the likelihood of cardiac electrical abnormalities. Ion channels can also be upor down-regulated in congenital heart disease, altering action potential cellular properties and therefore triggering arrhythmias. Conduction velocities may be inhomogeneously altered if connexin function, density or distribution changes. Another important group of electrophysiologic diseases is the heterogeneous category of inherited arrhythmias in the structurally normal heart, with a propensity to sudden cardiac death. There have been many recent relevant discoveries that help explain the molecular and functional mechanisms of long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and other electrical myopathies. Identification of molecular pathways allows the identification of new therapeutic targets, for both disease palliation and cure. As more disease-causing mutations are identified and genotypic-phenotypic correlation is defined, families can be screened prior to symptom-onset and patients may potentially be treated in a genotype-specific manner, opening the doors of cardiac electrophysiology to the emerging field of pharmacogenomics.
Export Options
About this article
Cite this article as:
Wolf M. Cordula and Berul I. Charles, Molecular Mechanisms of Inherited Arrhythmias, Current Genomics 2008; 9 (3) . https://dx.doi.org/10.2174/138920208784340768
DOI https://dx.doi.org/10.2174/138920208784340768 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Current Genomics in Cardiovascular Research
Cardiovascular diseases are the main cause of death in the world, in recent years we have had important advances in the interaction between cardiovascular disease and genomics. In this Research Topic, we intend for researchers to present their results with a focus on basic, translational and clinical investigations associated with ...read more
Deep learning in Single Cell Analysis
The field of biology is undergoing a revolution in our ability to study individual cells at the molecular level, and to integrate data from multiple sources and modalities. This has been made possible by advances in technologies for single-cell sequencing, multi-omics profiling, spatial transcriptomics, and high-throughput imaging, as well as ...read more
New insights on Pediatric Tumors and Associated Cancer Predisposition Syndromes
Because of the broad spectrum of children cancer susceptibility, the diagnosis of cancer risk syndromes in children is rarely used in direct cancer treatment. The field of pediatric cancer genetics and genomics will only continue to expand as a result of increasing use of genetic testing tools. It's possible that ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Asymmetric Dimethylarginine (ADMA): A Promising Biomarker for Cardiovascular Disease?
Current Topics in Medicinal Chemistry Calcium Related Genes in Dogs as Potential Cardiac Biomarkers for the Detection of Chronic Mitral Valve Disease
Recent Patents on Biomarkers Peripartum Cardiomyopathy: Moving Towards a More Central Role of Genetics
Current Cardiology Reviews Aging as an Evolvability-Increasing Program Which can be Switched Off by Organism to Mobilize Additional Resources for Survival
Current Aging Science Cellular Therapy for Myocardial Repair
Current Cardiology Reviews Allopurinol Hypersensitivity Reactions: Desensitization Strategies and New Therapeutic Alternative Molecules
Inflammation & Allergy - Drug Targets (Discontinued) Advances in Chagas Disease Chemotherapy
Anti-Infective Agents in Medicinal Chemistry Potential Targets for Intervention in Radiation-Induced Heart Disease
Current Drug Targets Mesenchymal Stem Cells: New Approaches for the Treatment of Neurological Diseases
Current Stem Cell Research & Therapy Diagnosis and Prognosis of Fetal Cardiomyopathies: A Review
Current Pharmaceutical Design Natural Alkaloids and Diabetes Mellitus: A Review
Endocrine, Metabolic & Immune Disorders - Drug Targets Utilization of Evidence-Based Secondary Prevention Medications at the Time of Discharge in Patients with Acute Coronary Syndrome (ACS) in Qatar
Current Vascular Pharmacology Endocarditis Due to Salmonella Enterica Subsp. Arizonae in a Patient with Sickle Cell Disease: A Case Report and Review of the Literature
Cardiovascular & Hematological Disorders-Drug Targets Bridging the Gap: The Potential Role of Corticosteroid Binding Globulin in Cardiac Steroid Facilitation
Current Drug Targets Genetic Polymorphism of Organic Anion and Cation Transporters: Pharmacokinetic and Pharmacodynamic Consequences in Pharmacotherapy
Current Pharmacogenomics Functional Relevance of Biased Signaling at the Angiotensin II Type 1 Receptor
Endocrine, Metabolic & Immune Disorders - Drug Targets Mitochondrial Dysfunction and Oxidative Stress in Insulin Resistance
Current Pharmaceutical Design Beyond the Cardiac Myofilament: Hypertrophic Cardiomyopathy- Associated Mutations in Genes that Encode Calcium-Handling Proteins
Current Molecular Medicine Glucocorticoid Excess Induces Accumulation of Cardiac Glycogen and Triglyceride: Suggested Role for AMPK
Current Pharmaceutical Design Induction of Myocardial Fibrosis and Hypertrophy by Natriuretic Peptides
Vascular Disease Prevention (Discontinued)