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
Advanced AI Techniques in Big Genomic Data Analysis
The thematic issue on "Advanced AI Techniques in Big Genomic Data Analysis" aims to explore the cutting-edge methodologies and applications of artificial intelligence (AI) in the realm of genomic research, where vast amounts of data pose both challenges and opportunities. This issue will cover a broad spectrum of AI-driven strategies, ...read more
Applications of Single-cell Sequencing Technology in Reproductive Medicine
Single cell sequencing (SCS) technology utilizes individual cells' genetic material to sequence their genome, transcriptome, and epigenetics at the molecular level. It offers insights into cell heterogeneity and enables the study of limited biological materials. Since its recognition as a valuable technique in 2011, single cell sequencing has yielded numerous ...read more
Big Data in Cancer Research
Cancer is a significant threat to human life and health, remaining a highly aggressive killer. It is a leading cause of death worldwide and represents a crucial medical issue for humanity. However, in the past decade, the effectiveness of new synthetic anticancer agents has not matched the current clinical speculation. ...read more
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
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
-
Phenotypic Screening for Pharmaceuticals Using Tissue Constructs
Current Pharmaceutical Biotechnology Biomarkers of Atrial Fibrillation in Hypertension
Current Medicinal Chemistry Expression of microRNAs (133b and 138) and Correlation with Echocardiographic Parameters in Patients with Alcoholic Cardiomyopathy
MicroRNA Chemo-drug Controlled-release Strategies of Nanocarrier in the Development of Cancer Therapeutics
Current Medicinal Chemistry Oxidative Stress on Progenitor and Stem Cells in Cardiovascular Diseases
Current Pharmaceutical Biotechnology Selenium Containing Compounds from Poison to Drug Candidates: A Review on the GPx-like Activity
Current Chemical Biology Measurement of the Endogenous Adenosine Concentration in Humans In Vivo: Methodological Considerations
Current Drug Metabolism Viral Myocarditis and Dilated Cardiomyopathy: Etiology and Pathogenesis
Current Pharmaceutical Design Role of Non-Coding RNA of Human Platelet in Cardiovascular Disease
Current Medicinal Chemistry The Anti-fibrotic Hormone Relaxin is not Reno-protective, Despite Being Active, in an Experimental Model of Type 1 Diabetes
Protein & Peptide Letters Endoplasmic Reticulum Stress as a Novel Therapeutic Target in Heart Diseases
Cardiovascular & Hematological Disorders-Drug Targets Patent Selections
Recent Patents on Cardiovascular Drug Discovery Role of Nitrosative Stress and Poly(ADP-ribose) Polymerase Activation in Diabetic Vascular Dysfunction
Current Vascular Pharmacology Dietary Fatty Acids in Metabolic Syndrome, Diabetes and Cardiovascular Diseases
Current Diabetes Reviews PREFACE: Cardiovascular and Hematological Medicine in 2015 - Advances and Insights
Cardiovascular & Hematological Agents in Medicinal Chemistry Ryanodine Receptor - A Novel Therapeutic Target in Heart Disease
Recent Patents on Cardiovascular Drug Discovery Urotensin-II Receptor: A Double Identity Receptor Involved in Vasoconstriction and in the Development of Digestive Tract Cancers and other Tumors
Current Cancer Drug Targets Targeting Apelinergic System in Cardiometabolic Disease
Current Drug Targets Outcomes of Patients with Chronic Heart Failure and Iron Deficiency Treated with Intravenous Iron: A Meta-analysis
Cardiovascular & Hematological Disorders-Drug Targets The Impact of Traditional Chinese Medicine on Mitophagy in Disease Models
Current Pharmaceutical Design