Abstract
The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play an important role in the generation of pacemaker activity of cardiac sinoatrial node cells and immature cardiomyocytes. HCN channels are also present in adult atrial and ventricular cardiomyocytes, where the physiological role is currently under investigation. In different cardiac pathologies, dysfunctional HCN channels have been suggested to be a direct cause of rhythm disorders. While loss-of-function mutations of HCN channels are associated with sinus bradycardia, HCN channel gain-of-function in atrial fibrillation, ventricular hypertrophy and failure might help enhance ectopic electrical activity and promote arrhythmogenesis. Blockade of HCN channels with ivabradine, a selective bradycardic agent currently available for clinical use, improves cardiac performance and counteracts functional remodeling in experimental hypertrophy. Accordingly, ivabradine ameliorates clinical outcome in patients with chronic heart failure. Novel compounds with enhanced selectivity for cardiac HCN channel isoforms are being studied as potential candidates for new drug development.
Keywords: Arrhythmias, atrioventricular node, cardiac hypertrophy, cardiomyocytes, HCN channels, sinoatrial node.
Current Drug Targets
Title:Updates on HCN Channels in the Heart: Function, Dysfunction and Pharmacology
Volume: 16 Issue: 8
Author(s): Laura Sartiani, Maria Novella Romanelli, Alessandro Mugelli and Elisabetta Cerbai
Affiliation:
Keywords: Arrhythmias, atrioventricular node, cardiac hypertrophy, cardiomyocytes, HCN channels, sinoatrial node.
Abstract: The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play an important role in the generation of pacemaker activity of cardiac sinoatrial node cells and immature cardiomyocytes. HCN channels are also present in adult atrial and ventricular cardiomyocytes, where the physiological role is currently under investigation. In different cardiac pathologies, dysfunctional HCN channels have been suggested to be a direct cause of rhythm disorders. While loss-of-function mutations of HCN channels are associated with sinus bradycardia, HCN channel gain-of-function in atrial fibrillation, ventricular hypertrophy and failure might help enhance ectopic electrical activity and promote arrhythmogenesis. Blockade of HCN channels with ivabradine, a selective bradycardic agent currently available for clinical use, improves cardiac performance and counteracts functional remodeling in experimental hypertrophy. Accordingly, ivabradine ameliorates clinical outcome in patients with chronic heart failure. Novel compounds with enhanced selectivity for cardiac HCN channel isoforms are being studied as potential candidates for new drug development.
Export Options
About this article
Cite this article as:
Sartiani Laura, Romanelli Novella Maria, Mugelli Alessandro and Cerbai Elisabetta, Updates on HCN Channels in the Heart: Function, Dysfunction and Pharmacology, Current Drug Targets 2015; 16 (8) . https://dx.doi.org/10.2174/1389450116666150531152047
DOI https://dx.doi.org/10.2174/1389450116666150531152047 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
- 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
Related Articles
-
Nanocarriers for Tracking and Treating Diseases
Current Medicinal Chemistry Pharmacological Therapy in Children with Atrial Fibrillation and Atrial Flutter
Current Pharmaceutical Design The Role of Minocycline in Ischemia-Reperfusion Injury: A Comprehensive Review of an Old Drug with New Implications
Recent Patents on Cardiovascular Drug Discovery The Discovery and Development of Drug Combinations for the Treatment of Various Diseases from Patent Literature (1980-Present)
Current Topics in Medicinal Chemistry Antioxidants in the Practice of Medicine; What Should the Clinician Know?
Cardiovascular & Hematological Disorders-Drug Targets Statins and Contrast-Induced Nephropathy: A Systematic Review and Meta-Analysis
Current Pharmaceutical Design Harnessing the Potential of Long Non-coding RNAs to Manage Metabolic Diseases
Current Pharmaceutical Design Recent Advancement in the Treatment of Cardiovascular Diseases: Conventional Therapy to Nanotechnology
Current Pharmaceutical Design The Versatile Stress Protein Mortalin as a Chaperone Therapeutic Agent
Protein & Peptide Letters A Common Molecular Motif Characterizes Extracellular Allosteric Enhancers of GPCR Aminergic Receptors and Suggests Enhancer Mechanism of Action
Current Medicinal Chemistry In vivo Optical Molecular Imaging of Cardiovascular Diseases: Long Road Ahead
Current Molecular Imaging (Discontinued) Heart Failure
Current Hypertension Reviews Decreased Vascular Repair and Neovascularization with Ageing: Mechanisms and Clinical Relevance with an Emphasis on Hypoxia- Inducible Factor-1
Current Molecular Medicine Inhibitors of the Ubiquitin-Proteasome System and the Cell Death Machinery: How Many Pathways are Activated?
Current Molecular Pharmacology Amiodarone Hepatotoxicity
Current Vascular Pharmacology Role of Non-Coding RNA of Human Platelet in Cardiovascular Disease
Current Medicinal Chemistry Flavonoids and Anthranquinones as Xanthine Oxidase and Monoamine Oxidase Inhibitors: A New Approach Towards Inflammation and Oxidative Stress
Current Topics in Medicinal Chemistry Toll Like Receptors Signaling Pathways as a Target for Therapeutic Interventions
Current Signal Transduction Therapy Molecular and Clinical Aspects of the Target Therapy with the Calcimimetic Cinacalcet in the Treatment of Parathyroid Tumors
Current Cancer Drug Targets Vitamin D and the Adaptive Immune System with Special Emphasis to Allergic Reactions and Allograft Rejection
Inflammation & Allergy - Drug Targets (Discontinued)