Abstract
The spontaneous activity of cardiac tissue originates in specialized pacemaker cells in the sino-atrial node that generate autonomous rhythmic electrical impulses. A number of regions in the brain are also able to generate spontaneous rhythmic activity to control and regulate important physiological functions. The generation of pacemaker potentials relies on a complex interplay between different types of currents carried by cation channels. Among these currents, the hyperpolarization-activated current (termed If, cardiac pacemaker “funny” current, and Ih in neurons) is the major component contributing to the initiation of cardiac and neuronal excitability and to the modulation of this excitability by neurotransmitters and hormones. If is an inward current activated by hyperpolarization of the membrane potential and by intracellular cyclic nucleotides such as cAMP. The identification at the end of the 1990s of a family of mammalian genes that encode for four Hyperpolarization-activated Cyclic Nucleotide- gated channels, HCN1-4, has made analysis of the location of these channels and the study of their biophysical properties an obtainable goal. As a result, specific agents have been developed for their ability to selectively reduce heart rate by lowering cardiac pacemaker activity where f-channels are their main natural target. These drugs include alinidine, zatebradine, cilobradine, ZD-7288 and ivabradine. Recent data indicate that pharmacological tools such as W7 and genistein, which have been used to identify some intracellular pathways involved in ionic channel modulation, also have the ability to inhibit If directly. This opens new perspectives for the future development of other specific rhythm-lowering agents.
Keywords: HCN, If Current, bradycardic agents, pacemaker, heart, brain
Current Pharmaceutical Design
Title: Molecular Regulation and Pharmacology of Pacemaker Channels
Volume: 13 Issue: 23
Author(s): Patrick Bois, Romain Guinamard, Antoun E.L. Chemaly, Jean-Francois Faivre and Jocelyn Bescond
Affiliation:
Keywords: HCN, If Current, bradycardic agents, pacemaker, heart, brain
Abstract: The spontaneous activity of cardiac tissue originates in specialized pacemaker cells in the sino-atrial node that generate autonomous rhythmic electrical impulses. A number of regions in the brain are also able to generate spontaneous rhythmic activity to control and regulate important physiological functions. The generation of pacemaker potentials relies on a complex interplay between different types of currents carried by cation channels. Among these currents, the hyperpolarization-activated current (termed If, cardiac pacemaker “funny” current, and Ih in neurons) is the major component contributing to the initiation of cardiac and neuronal excitability and to the modulation of this excitability by neurotransmitters and hormones. If is an inward current activated by hyperpolarization of the membrane potential and by intracellular cyclic nucleotides such as cAMP. The identification at the end of the 1990s of a family of mammalian genes that encode for four Hyperpolarization-activated Cyclic Nucleotide- gated channels, HCN1-4, has made analysis of the location of these channels and the study of their biophysical properties an obtainable goal. As a result, specific agents have been developed for their ability to selectively reduce heart rate by lowering cardiac pacemaker activity where f-channels are their main natural target. These drugs include alinidine, zatebradine, cilobradine, ZD-7288 and ivabradine. Recent data indicate that pharmacological tools such as W7 and genistein, which have been used to identify some intracellular pathways involved in ionic channel modulation, also have the ability to inhibit If directly. This opens new perspectives for the future development of other specific rhythm-lowering agents.
Export Options
About this article
Cite this article as:
Patrick Bois , Romain Guinamard , Antoun E.L. Chemaly , Jean-Francois Faivre and Jocelyn Bescond , Molecular Regulation and Pharmacology of Pacemaker Channels, Current Pharmaceutical Design 2007; 13 (23) . https://dx.doi.org/10.2174/138161207781368729
DOI https://dx.doi.org/10.2174/138161207781368729 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
Platelets and Platelet Interaction with Progenitor Cells in Vascular Homeostasis and Inflammation
Current Vascular Pharmacology “Letting the Air In” Can Set the Stage for Tumor Recurrences
Current Cancer Therapy Reviews The Effect of Serotonin 5-HT2 Receptor Inhibitor on Vasomotor Responses
Vascular Disease Prevention (Discontinued) Cell Metabolism Under Microenvironmental Low Oxygen Tension Levels in Stemness, Proliferation and Pluripotency
Current Molecular Medicine Circadian MicroRNAs in Cardioprotection
Current Pharmaceutical Design Levosimendan: A Novel Agent in Heart Failure
Recent Patents on Cardiovascular Drug Discovery Selective Removal of Macrophages in Atherosclerotic Plaques as a Pharmacological Approach for Plaque Stabilization: Benefits Vs. Potential Complications
Current Vascular Pharmacology Factors Modulating Fibrates Response: Therapeutic Implications and Alternative Strategies
Endocrine, Metabolic & Immune Disorders - Drug Targets Cardiovascular disease management through restrained inflammatory responses
Current Pharmaceutical Design Approaches to the Management of Acute Kidney Injury in Children
Recent Patents on Biomarkers Remodeling of the Myocardium and Potential Targets in the Collagen Degradation and Synthesis Pathways
Current Drug Targets - Cardiovascular & Hematological Disorders Coronary Risk Assessment and Management Options in Chronic Kidney Disease Patients Prior to Kidney Transplantation
Current Cardiology Reviews Regulation of the Cardiac Sodium/Bicarbonate Cotransporter by Angiotensin II: Potential Contribution to Structural, Ionic and Electrophysiological Myocardial Remodelling
Current Cardiology Reviews Radiolabeled Compounds in Diagnosis of Infectious and Inflammatory Disease
Current Pharmaceutical Design Repetitive Transient Phosphodiesterase-3 Inhibition Eliminates Non-ischemic Cardiac Remodeling and Failure
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) MicroRNAs: A Critical Regulator and a Promising Therapeutic and Diagnostic Molecule for Diabetic Cardiomyopathy
Current Gene Therapy Anesthetic Cardioprotection in Clinical Practice From Proof-of-Concept to Clinical Applications
Current Pharmaceutical Design Endothelin Receptor Antagonists as Disease Modifiers in Systemic Sclerosis
Inflammation & Allergy - Drug Targets (Discontinued) Adipose-Derived Stromal/Stem Cells (ASC) in Regenerative Medicine: Pharmaceutical Applications
Current Pharmaceutical Design Systemic Sclerosis: Clinical Manifestations
Current Rheumatology Reviews