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
-
Novel Genetic and Peptide-Based Strategies Targeting the Bcl-2 Family, an Update
Recent Patents on DNA & Gene Sequences Measurement of Extravascular Lung Water in Critically Ill Patients
Current Respiratory Medicine Reviews Endocannabinoid Regulation of Matrix Metalloproteinases: Implications in Ischemic Stroke
Cardiovascular & Hematological Agents in Medicinal Chemistry P2Y12 Receptor Antagonists in Acute Coronary Syndrome: Clinical Implications of Pharmacologic and Pharmacogenetic Differences
Recent Patents on Cardiovascular Drug Discovery microRNA Regulation as a Therapeutic Strategy for Cardiovascular Disease
Current Drug Targets Toxicities of Targeted Agents in Advanced Renal Cell Carcinoma
Current Clinical Pharmacology Gender Bias in Acute Coronary Syndromes
Current Vascular Pharmacology Editorial (Thematic Issue: Multidisciplinary Imaging of the Coronary Circulation: A Fast Moving Field)
Recent Patents on Medical Imaging Nanoceria: Synthesis and Biomedical Applications
Current Nanoscience Does Caffeine Affect Cardiovascular Responses?
Vascular Disease Prevention (Discontinued) Current Drug Nano-targeting Strategies for Improvement in the Diagnosis and Treatment of Prevalent Pathologies such as Cardiovascular and Renal Diseases
Current Drug Targets Folic Acid, Neurodegenerative and Neuropsychiatric Disease
Current Molecular Medicine Nano- and Biotechnological Approaches in Current and Future Generation of Cardiovascular Stents
Current Nanoscience Oral Antiplatelet Therapy for Acute Coronary Syndromes: Aspirin, P2Y12 Inhibition and Thrombin Receptor Antagonists
Current Drug Targets Genomics and the Prospects of Existing and Emerging Therapeutics for Cardiovascular Diseases
Current Pharmaceutical Design Chronopharmaceutical Delivery of Anti-Inflammatory Drugs
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Endothelin and the Ischaemic Heart
Current Vascular Pharmacology Biological Consequences of Dysfunctional HDL
Current Medicinal Chemistry Patent Selections
Recent Patents on Cardiovascular Drug Discovery Calcium Related Genes in Dogs as Potential Cardiac Biomarkers for the Detection of Chronic Mitral Valve Disease
Recent Patents on Biomarkers